INHIBITORS OF PROTEIN METHYLTRANSFERASE DOT1L AND METHODS OF USE THEREOF

Abstract

The present invention relates to DOT1L inhibitors and methods of identifying, designing, or optimizing them. The present invention also relates to crystals of DOT1L-inhibitor complexes, the crystal structures thereof, and the use of the crystal structures. Also disclosed are pharmaceutical compositions containing these DOT1L inhibitors and methods of treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Description

SUMMARY OF THE INVENTION

The invention is based upon the discovery that a surprising conformational adaptation results in high-affinity inhibitor binding of aminonucleoside inhibitors of DOT1L to the enzyme and prolonged residence time.

The invention provides compounds useful for selectively inhibiting DOT1L. The present invention also provides pharmaceutically acceptable salts, esters, and/or N-oxides, of these compounds.

The invention further features a method for designing, identifying, and/or optimizing a candidate DOT1L inhibitor.

In one aspect, the invention features a compound of Formula (I) below or a pharmaceutically acceptable salt or ester thereof:

wherein,

Nuc is adenosine-like moiety or an analog or a derivative thereof,

T is a linker group of a 6-10 carbon atoms, in which one or more carbon atoms are optionally replaced with a heteroatom and T is optionally substituted;

Nuc-T is capable of binding within the SAM binding pocket of human DOT1L which comprises amino acid residues 135-241 of SEQ ID NO: 1; and

R₉ is a group such that R₉ induces a conformational adaptation in human DOT1L, wherein the conformational adaptation is the formation of a hydrophobic pocket domain which comprises amino acid residues 139-312 of SEQ ID NO: 1; and

further wherein Nuc-T is capable of binding within the SAM binding pocket of human DOT1L which comprises amino acid residues 135-241 of SEQ ID NO: 1.

In another aspect, the invention features a method for designing and/or identifying a potential binding compound for protein DOT1L. The method comprises:

(a) generating, on a computer, a three-dimensional structure of DOT1L having the structural coordinates of Table S1 or S2;

• • (b) identifying amino acid residues forming an hydrophobic pocket site in the three-dimensional structure of DOT1L from step (a), wherein the hydrophobic pocket domain of DOT1L is characterized by the crystallography coordinates of human DOT1L amino acids Leu143, Met147, Phe239, and Tyr312 according to Table S1 or S2;

(c) generating a three-dimensional model of the active site;

(d) designing and/or selecting a compound that potentially binds to the active site using the three-dimensional model of the active site; and

(e) synthesizing and/or choosing the potential binding compound.

In yet another aspect, the invention features a method for designing and/or identifying a potential binding compound for protein DOT1L, the method comprising computationally identifying a binding compound that binds to DOT1L using the atomic coordinates of Leu143, Met147, Phe239, and Tyr312 according to Table S1 or S2.

In still another aspect, the invention features a method for designing and/or identifying a potential binding compound for protein DOT1L, the method comprising:

a) providing a set of atomic coordinates for human DOT1L as set forth in Table S1 or S2; and

• • b) identifying in silico a binding compound that binds to DOT1L using the coordinates of step (a).

The invention also features a method of identifying a drug candidate for the treatment of a disease, the method comprising:

a) using the atomic coordinates set forth in Table S1 or S2 to form a three-dimensional structure of DOT1L;

b) selecting a test compound having the best fit with the structure of DOT1L; and

c) assaying the ability of the test compound to modulate DOT1L activity, wherein a test compound that modulates DOT1L activity is considered a drug candidate for treating a disease.

In another aspect, the invention features a DOT1L inhibitor having molecular dimensions compatible with the shape of a hydrophobic pocket domain of DOT1L characterized by the crystallography coordinates of human DOT1L amino acids Leu143, Met147, Phe239, and Tyr312, according to Table S1 or S2, wherein the compound has a biochemical IC₅₀ for DOT1L of less than 100 nM.

The invention also features a computer readable medium comprising the atomic coordinates of one or more DOT1L-Compound A2, DOT1L-Compound C1, DOT1L-Compound C118 and DOT1L-Compound D16.

The invention also features a method for designing, identifying, and/or optimizing a candidate DOT1L inhibitor compound or complex. The method comprises:

(a) generating a crystal structure, a three-dimensional model of DOT1L, or obtaining the structure coordinates of DOT1L in complex with the candidate DOT1L inhibitor compound or complex, and

(b) determining if the candidate DOT1L inhibitor compound or complex induces a conformational adaptation and/or a hydrophobic binding site of the DOT1L from the three-dimensional model.

In yet another aspect, the invention features a method for designing, identifying, and/or optimizing a candidate DOT1L inhibitor compound or complex that interacts with all or a part of a hydrophobic pocket domain which comprises amino acid residues 139-312 of SEQ ID NO: 1 and the SAM binding pocket of human DOT1L which comprises amino acid residues 135-241 of SEQ ID NO: 1. The method includes

(a) producing the structure coordinates of the hydrophobic binding pocket of DOT1L in silico comprising the means for generating three-dimensional structural information from the coordinates;

(b) designing, selecting and/or optimizing the candidate DOT1L inhibitor compound or complex by performing a fitting operation between the candidate DOT1L inhibitor compound or complex and the three-dimensional structural information of all or part of the hydrophobic binding pocket or DOT1L protein; and

(c) optionally employing computerized and/or reiterative steps.

The invention also relates to a pharmaceutical composition of a compound of Formula (I) and a pharmaceutically acceptable carrier.

The invention also relates to a pharmaceutical composition comprising a DOT1L inhibitor designed, identified, and/or optimized by the method disclosed herein and a pharmaceutically acceptable carrier.

The invention also relates to a pharmaceutical composition of a salt of a compound of Formula (I) or a salt of a DOT1L inhibitor designed, identified, and/or optimized by the method disclosed herein and a pharmaceutically acceptable carrier.

The invention also relates to a pharmaceutical composition of a hydrate of a compound of Formula (I) or a hydrate of a DOT1L inhibitor designed, identified, and/or optimized by the method disclosed herein and a pharmaceutically acceptable carrier.

The present invention provides methods of treating or preventing cancer. The present invention provides methods of treating cancer. The present invention also provides methods of preventing cancer. The method includes administering to a subject in need thereof a therapeutically effective amount of the compound of Formula (I) or a therapeutically effective amount of a DOT1L inhibitor designed, identified, and/or optimized by the method disclosed herein. The cancer can be a hematological cancer. Preferably, the cancer is leukemia. More preferably, the cancer is acute myeloid leukemia, acute lymphocytic leukemia or mixed lineage leukemia.

The present invention provides methods of treating or preventing a disease or disorder mediated by translocation of a gene on chromosome 11q23. The present invention provides methods of treating a disease or disorder mediated by translocation of a gene on chromosome 11q23. The present invention also provides methods of preventing a disease or disorder mediated by translocation of a gene on chromosome 11q23. The method includes administering to a subject in need thereof a therapeutically effective amount of the compound of Formula (I) or a therapeutically effective amount of a DOT1L inhibitor designed, identified, and/or optimized by the method disclosed herein.

The present invention provides methods of treating or preventing a disease or disorder in which DOT1-mediated protein methylation plays a part or a disease or disorder mediated by DOT1-mediated protein methylation. The present invention provides methods of treating a disease or disorder in which DOT1-mediated protein methylation plays a part or a disease or disorder mediated by DOT-mediated protein methylation. The present invention also provides methods of preventing a disease or disorder in which DOT1-mediated protein methylation plays a part or a disease or disorder mediated by DOT1-mediated protein methylation. The method includes administering to a subject in need thereof a therapeutically effective amount of the compound of Formula (I) or a therapeutically effective amount of a DOT1L inhibitor designed, identified, and/or optimized by the method disclosed herein.

The present invention provides methods of inhibiting DOT1L activity in a cell. The method includes contacting the cell with an effective amount of one or more of the compound of Formula (I) or one or more of the DOT1L inhibitor designed, identified, and/or optimized by the method disclosed herein.

Still another aspect of the invention relates to a method of reducing the level of Histone H3 Lysine residue 79 (H3-K79) methylation in a cell. The method includes contacting a cell with a compound of the present invention. Such method can be used to ameliorate any condition which is caused by or potentiated by the activity of DOT1 through H3-K79 methylation.

The present invention relates to use of the compounds disclosed herein in preparation of a medicament for treating or preventing cancer. The use includes a compound of Formula (I) for administration to a subject in need thereof in a therapeutically effective amount. The cancer can be a hematological cancer. Preferably, the cancer is leukemia. More preferably, the cancer is acute myeloid leukemia, acute lymphocytic leukemia or mixed lineage leukemia.

The present invention provides use of the compounds disclosed herein in preparation of a medicament for treating or preventing a disease or disorder mediated by translocation of a gene on chromosome 11q23. The use includes a compound of Formula (I) or a DOT1L inhibitor designed, identified, and/or optimized by the method disclosed herein for administration to a subject in need thereof in a therapeutically effective amount.

The present invention provides use of the compounds disclosed herein in preparation of a medicament for treating or preventing a disease or disorder in which DOT1-mediated protein methylation plays a part or a disease or disorder mediated by DOT1-mediated protein methylation. The use includes a compound of Formula (I) or a DOT1L inhibitor designed, identified, and/or optimized by the method disclosed herein for administration to a subject in need thereof in a therapeutically effective amount.

The present invention provides use of the compounds disclosed herein for inhibiting DOT1L activity in a cell. The use includes contacting the cell with an effective amount of one or more of the compound of Formula (I) and/or the DOT1L inhibitor designed, identified, and/or optimized by the method disclosed herein.

Still another aspect of the invention relates to a use of the compounds disclosed herein for reducing the level of Histone H3 Lysine residue 79 (H3-K79) methylation in a cell. The use includes contacting a cell with a compound of the present invention. Such use can ameliorate any condition which is caused by or potentiated by the activity of DOT1 through H3-K79 methylation.

In the formulae presented herein, the variables can be selected from the respective groups of chemical moieties later defined in the detailed description.

In addition, the invention provides methods of synthesizing the foregoing compounds. Following synthesis, a therapeutically effective amount of one or more of the compounds can be formulated with a pharmaceutically acceptable carrier for administration to a mammal, particularly humans, for use in modulating an epigenetic enzyme. In certain embodiments, the compounds of the present invention are useful for treating, preventing, or reducing the risk of cancer or for the manufacture of a medicament for treating, preventing, or reducing the risk of cancer. Accordingly, the compounds or the formulations can be administered, for example, via oral, parenteral, otic, ophthalmic, nasal, or topical routes, to provide an effective amount of the compound to the mammal.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In the specification, the singular forms also include the plural unless the context clearly dictates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents and other references mentioned herein are incorporated by reference. The references cited herein are not admitted to be prior art to the claimed invention. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods and examples are illustrative only and are not intended to be limiting.

Other features and advantages of the invention will be apparent from the following detailed description and claims.

DESCRIPTION OF THE FIGURES

FIG. 1 is a plot showing that Compound A2 causes complete and sustained tumor regression in a MV4-11 nude rat xenograft model of MLL-rearranged leukemia.

FIG. 2 includes plots showing biochemical characterization of Compound D16 inhibition of DOT1L. (A) Compound D16 is a competitive inhibitor with respect to SAM. The IC₅₀ of Compound D16 was determined as a function of SAM concentration relative to the K_m of SAM ([SAM]/K_m) and found to display a linear relationship as expected for competitive inhibition. Inset: Michaelis-Menten plot of product formation as a function of SAM concentration at various concentrations of Compound D16. The data were fit globally to a general equation for enzyme inhibition (Copeland R A, Evaluation of enzyme inhibitors in drug discovery. A guide for medicinal chemists and pharmacologists. New York: Wiley; 2005) and yield values of alpha of 10±6 and K_i of 0.3±0.03 nM. (B) Compound D16 is a noncompetitive inhibitor with respect to oligonucleosome (Nucl). The IC₅₀ of Compound D16 was determined as a function of Nuc concentration relative to the K_m of Nucl ([Nucl]/K_m) and found to be independent of [Nucl]/K_m, as expected for noncompetitive inhibition. Inset: Michaelis-Menten plot of product formation as a function of Nuc concentration at various concentrations of Compound D16. The data were fit globally to a general equation for enzyme inhibition (Copeland, 2005) and yield values of alpha of 0.5±0.2 and K_i of 0.3±0.02 nM.

FIG. 3 is a plot showing superposition of SAM and Compound C1 within the active site of DOT1L, demonstrating conservation of binding motif. DOT1L-SAM co-crystal structure (PDB code: 3QOW): in line presentation (carbon atoms: light blue; oxygen: red; nitrogen: dark blue). SAM: stick presentation (carbon atoms: light blue; oxygen: red; nitrogen: dark blue, sulfur: yellow). Compound C1: stick presentation (carbon atoms: maroon; oxygen: red; nitrogen: dark blue). Hydrogen bonds between SAM and DOT1L are labeled by dashed lines.

FIG. 4A shows key contacts between DOT1L protein and the urea moiety of Compound C118 in the DOT1L-Compound C118 co-crystal structure. SAM is superimposed on to Compound C118. The interactions for 5′-amino and urea of Compound C118 are labeled by dashed lines. DOT1L protein of the DOT1L-Compound C118 co-crystal structure: in line presentation (carbon atoms: green; oxygen: red; nitrogen: dark blue). Compound C118: stick presentation (carbon atoms: green). SAM: stick presentation (carbon atoms: light blue)

FIG. 4B shows opening of the hydrophobic pocket within the DOT1L-Compound C118 co-crystal structure. Superimposition of DOT1L-SAM and DOT1L-Compound C118 demonstrates the opening of the hydrophobic pocket by the tert-butyl phenyl group on Compound C118. DOT1L structures are presented in Ca trace. The key residue side chains which open the pocket are displayed as in line presentation. Comparison of these residues in the DOT1L-SAM and DOT1L-Compound C118 structures shows the conformational change and resultant opening of the hydrophobic pocket upon the binding of Compound C118. DOT1L protein: in line presentation (carbon atoms: green for the DOT1L-Compound C118 structure and light blue for the DOT1L-SAM structure; oxygen: red; nitrogen: dark blue). Compound C118: stick presentation (carbon atoms: green). SAM: stick presentation (carbon atoms: light blue)

FIG. 4C shows loop disorder induced by binding of Compound C118 to DOT1L. Superimposition of DOT1L-SAM and DOT1L-Compound C118 shows the disorder in 130s' and 300s' loops upon the binding of Compound C118. DOT1L protein: in line presentation (carbon atoms: green for the DOT1L-Compound C118 structure and light blue for the DOT1L-SAM structure). Compound C118: stick presentation (carbon atoms: green; oxygen: red; nitrogen: dark blue). SAM: stick presentation (carbon atoms: light blue; oxygen: red; nitrogen: dark blue; sulfur: yellow)

FIG. 5 is superimposition of Compound D16 and Compound C118 structures. The DOT1L protein of DOT1L-Compound D16 is in surface presentation in grey. Compound D16 (carbon atoms: magenta) is superimposed with Compound C118 (carbon atoms: green).

FIG. 6 is a ligand plot to show the binding pockets of DOT1L in complex with Compound A2.

FIG. 7 is a ligand plot to show the binding pockets of DOT1L in complex with Compound D16.

FIG. 8 is a ligand plot to show the binding pockets of DOT1L in complex with Compound D8.

FIG. 9 is a ligand plot to show the binding pockets of DOT1L in complex with Compound C118.

FIG. 10 is a series of images showing 2Fo-Fc maps for Compounds C1 (A), C118 (B) and D16 (C). All maps were contoured at 1 σ.

DETAILED DESCRIPTION OF THE INVENTION

Certain aspects of the present invention provide compounds that can be used to selectively modulate the aberrant action of an epigenetic enzyme. Further, the compounds can be used to treat or prevent a disease state in a mammal caused or mediated by aberrant action of an epigenetic enzyme. The present invention includes pharmaceutically acceptable salts, esters, tautomers, and N-oxides of these compounds. Certain aspects of the present invention also provide methods of designing, identifying, and/or optimizing novel compounds as DOT1L inhibitors, synthetic methods for making the compounds, pharmaceutical compositions containing them and various uses of the compounds.

One aspect of the present invention relates to compounds that selectively modulate the activity of the histone methyltransferase DOT1L, an enzyme known to methylate lysine 79 of histone H3 (“H3K79”) in vivo (Feng et al. (2002) Curr. Biol. 12:1052-1058). Similar to other HMTases, DOT1L contains a S-adenosylmethionine (SAM) binding site and uses SAM as a methyl donor. However, unlike other reported HMTases, the DOT1 polypeptides do not contain a SET domain.

DOT1L nucleic acid and polypeptides have previously been described (see, e.g., U.S. Patent Application Publication No. 2005-0048634 A1 (hereby incorporated by reference); Feng et al. (2002) Curr. Biol. 12:1052-1058; and Okada et al. (2005) Cell 121:167-78). The sequences of the human nucleic acid and protein have been deposited under GenBank Accession No. AF509504, which is hereby incorporated by reference in its entirety. Only the approximately 360 N-terminal amino acids of hDOT1L share significant sequence similarity with the yeast DOT1. In addition, DOT1 homologs from C. elegans (GenBank Accession Nos. NP510056 and CAA90610), Drosophila (GenBank Accession Nos. CG10272 and AAF54122), mouse (GenBank Accession No. XP125730), Anopheles gambiae (GenBank Accession No. EAA03558), and Neurospora crassa (GenBank Accession No. EAA33634) are available in public databases (the disclosures of which are incorporated by reference herein in their entireties). The SAM binding domain among these homologs is conserved (approximately 30-100% amino acid sequence identity and 50-100% amino acid similarity). Various aspects of the present invention can be practiced with any DOT1L polypeptide or nucleic acid.

The 2.5 angstrom resolution structure of a fragment of the hDOT1L protein containing the catalytic domain (amino acids 1-416; SEQ ID NO: 1) has been solved, and the atomic coordinates for amino acids 1-416 of hDOT1L have been determined and deposited in the RCSB database under ID code 1NW3 and described in the scientific literature (Min et al. (2003) Cell 112:711-723), the disclosures of both of which are incorporated herein by reference in their entireties. As an example, human DOT1L includes the protein comprising SEQ ID NO: 1 and variants thereof comprising at least about 70% amino acid sequence identity to SEQ ID NO: 1, or preferably 80%, 85%, 90% and 95% sequence identity to SEQ ID NO:1, or more preferably, at least about 95% or more sequence identity to SEQ ID NO:1.

It has recently been demonstrated that hDOT1L plays an important role in MLL-AF10-mediated leukemogenesis (Okada et al. (2005) Cell 121:167-78). It was also shown that mistargeting of hDOT1L to the Hoxa9 gene by MLL-AF10 results in H3K79 methylation and Hoxa9 upregulation which contributes to leukemic transformation (Okada et al. (2005) Cell 121:167-78). It was further demonstrated that the hDOT1L and MLL-AF10 interaction involves the OM-LZ (octapeptide motif-leucine zipper) region of AF10, required for MLL-AF10-mediated leukemic transformation (DiMartino et al. (2002) Blood 99:3780-5). It has also been shown that CALM-AF10 fusion appears to be both necessary and sufficient to mediate leukemogenesis in vitro and in vivo; that hDOT1L and its H3K79 methyltransferase activity are implicated in CALM-AF10-mediated leukemic transformation; and that the Hoxa5 gene is involved in CALM-AF10-mediated transformation (U.S. Patent Application Publication No. 2009-0061443 A1, which is hereby incorporated by reference in its entirety). Aberrant recruitment of DOT1L leading to deregulated gene expression may be a common feature of many other oncogenic MLL-fusion proteins. For example, the MLL fusion partners ENL, AF4, and AF9 are normally found in nuclear complexes with DOT1L (Bitoun et al. (2007) Hum. Mol. Genet. 16:92-106, Mueller et al. (2007) Blood 110:4445-54, Zhang et al. (2006) J. Biol. Chem. 281:18059-68), and altered H3K79 methylation profiles are a feature of murine and human MLL-AF4 leukemias (Krivstov et al. (2008) Cancer Cell 14:355-368).

The present disclosure presents the design and optimization of a series of aminonucleoside inhibitors of the PKMT DOT1L. Using the crystal structures of various aminonucleoside inhibitors bound to human DOT1L, the key recognition elements of ligand binding to the enzymatic active site have been systematically defined. Conformational adaptation is a common feature of enzyme catalysis and of high-affinity ligand interactions with enzymes. This is clearly the case with the potent aminonucleoside inhibitors of DOT1L. A novel hydrophobic pocket, immediately adjacent to the SAM binding site of the enzyme has been discovered by the applicants. It was opened up to accommodate the extended aminonucleoside compounds that had been originally designed to engage the lysine binding channel of the contiguous enzyme active site. This structural adaptation results in very high-affinity binding of aminonucleosides to the enzyme and provided new directions for inhibitor optimization. The conformational adaptation mechanism of inhibitor binding demonstrated for the aminonucleosides also results in extended residence time for the optimized members of this inhibitor series. For example, D16 displays a DOT1L enzyme residence time of sixty minutes, as measured by surface plasmon resonance. A long residence time on PMT targets, such as DOT1L, may prove to be of value in demonstrating durable pharmacology in patients.

The invention features a method of designing, identifying, and/or optimizing an inhibitor of DOT1L, e.g., an aminonucleoside DOT1L inhibitor. The designing of inhibitors can be initiated using mechanism-guided design principles, based on the DOT1L enzymatic reaction mechanism, and optimized through structure-guided approaches using iterative enzyme-inhibitor complex crystal structures. In embodiments, conformational adaptation of the enzyme active site attends potent inhibitor binding and this observation can be taken into account to develop a cogent structure-activity relationship (SAR) for active site-directed DOT1L inhibition. In one embodiment, this optimization process results in Compound D16, which is a picomolar inhibitor of DOT1L with exquisite selectivity for its target enzyme. Compound D16 has been shown to demonstrate potent and selective killing of MLL-rearranged leukemic cells, both in cell culture and in a highly aggressive disseminated mouse model of this disease. Thus, the methods described herein provide ways to identify, design, or optimize potent, selective small molecule inhibitors of DOT1L to affect selective killing of MLL-rearranged leukemias.

The method of the invention includes:

(a) generating, on a computer, a three-dimensional structure of DOT1L having the structural coordinates of Table S1 or S2;

(b) identifying amino acid residues forming an hydrophobic pocket site in the three-dimensional structure of DOT1L from step (a), wherein the hydrophobic pocket domain of DOT1L is characterized by the crystallography coordinates of human DOT1L amino acids Leu143, Met147, Phe239, and Tyr312 according to Table S1 or S2;

(c) generating a three-dimensional model of the active site;

(d) designing and/or selecting a compound that potentially binds to the active site using the three-dimensional model of the active site; and

(e) synthesizing and/or choosing the potential binding compound.

The method can further include contacting the identified candidate inhibitor with the DOT1L in order to determine the effect of the inhibitor on DOT1L enzymatic activity, e.g., by evaluating the residence time, K_i value, or in an in vivo study.

The invention also features a method of identifying a drug candidate for the treatment of a disease, the method comprising:

a) using the atomic coordinates set forth in Table S1 or S2 to form a three-dimensional structure of DOT1L;

b) selecting a test compound having the best fit with the structure of DOT1L; and

c) assaying the ability of the test compound to modulate DOT1L activity, wherein a test compound that modulates DOT1L activity is considered a drug candidate for treating a disease.

The invention also features a method for designing, identifying, and/or optimizing a candidate DOT1L inhibitor compound or complex. The method comprises:

(a) generating a crystal structure, a three-dimensional model of DOT1L, or obtaining the structure coordinates of DOT1L in complex with the candidate DOT1L inhibitor compound or complex, and

(b) determining if the candidate DOT1L inhibitor compound or complex induces a conformational adaptation and/or a hydrophobic binding site of the DOT1L from the three-dimensional model.

In another aspect, the invention features a method of locating a binding site of a candidate DOT1L inhibitor compound or complex that modulates the activity of human DOT1L.

The method comprises:

(a) obtaining X-ray diffraction data for a crystal of human DOT1L in complex with SAM or SAH or a compound of Formula (I);

(b) determining X-ray diffraction data for a crystal of human DOT1L in complex with candidate DOT1L inhibitor compound or complex or an analog or a derivative thereof;

(c) subtracting the X-ray diffraction data obtained in step (a) from the X-ray diffraction data obtained in step (b) to obtain the difference in the X-ray diffraction data;

(d) obtaining phases that correspond to X-ray diffraction data obtained in step (a);

(e) utilizing the phases obtained in step (d) and the difference in the X-ray diffraction data obtained in step (c) to compute a difference Fourier image of the candidate inhibitor; and

(f) locating the binding site of the candidate inhibitor to human DOT1L based on the computations obtained in step (e).

In the above method of locating a binding site, the crystal in step (a) includes human DOT1L in complex with SAM or SAH, or Compound D16 or A2. In one embodiment, the DOT1L-inhibitor complex in step (b) comprises the hydrophobic pocket domain which comprises amino acid residues 139-312 of SEQ ID NO: 1 and the SAM binding pocket which comprises amino acid residues 135-241 of SEQ ID NO: 1.

In yet another aspect, the invention features a method for designing, identifying, and/or optimizing a candidate DOT1L inhibitor compound or complex that interacts with all or a part of a hydrophobic pocket domain which comprises amino acid residues 139-312 of SEQ ID NO: 1 and the SAM binding pocket of human DOT1L which comprises amino acid residues 135-241 of SEQ ID NO: 1. The method includes

(a) producing the structure coordinates of the hydrophobic binding pocket of DOT1L in silico comprising the means for generating three-dimensional structural information from the coordinates;

(b) designing, selecting and/or optimizing the candidate DOT1L inhibitor compound or complex by performing a fitting operation between the candidate DOT1L inhibitor compound or complex and the three-dimensional structural information of all or part of the hydrophobic binding pocket or DOT1L protein; and

(c) optionally employing computerized and/or reiterative steps.

The methods above include one or more of the following features:

For example, the SAM binding pocket of human DOT1L is characterized by the crystallography coordinates of human DOT1L amino acids Asp161, Gly163, Glu 186, Asp222, and Asn241. For example, the crystallography coordinates are within about a root mean square deviation of not more than about 3 Å (e.g., not more than about 2.5 Å, not more than about 2 Å, or not more than about 1.5 Å) from the backbone atoms of the amino acids according to Table S1 or S2.

For example, the SAM binding pocket of human DOT1L is characterized by the crystallography coordinates of human DOT1L amino acids Val135, Thr139, Asp161, Gly163, Gln168, Glu 186, Asp222, and Asn241. For example, the crystallography coordinates are within about a root mean square deviation of not more than about 3 Å (e.g., not more than about 2.5 Å, not more than about 2 Å, or not more than about 1.5 Å) from the backbone atoms of the amino acids according to Table S1 or S2. The SAM binding pocket of human DOT1L is further characterized by the crystallography coordinates of human DOT1L amino acid Phe223, for example, the crystallography coordinates are within about a root mean square deviation of not more than about 3 Å (e.g., not more than about 2.5 Å, not more than about 2 Å, or not more than about 1.5 Å) from the backbone atoms of the amino acid according to Table S1 or S2.

For example, the hydrophobic pocket domain of human DOT1L is characterized by the crystallography coordinates of human DOT1L amino acids Leu143, Met147, Phe239, and Tyr 312, for example, the crystallography coordinates are within about a root mean square deviation of not more than about 3 Å (e.g., not more than about 2.5 Å, not more than about 2 Å, or not more than about 1.5 Å) from the backbone atoms of the amino acids according to Table S1 or S2. The hydrophobic pocket domain of human DOT1L is further characterized by the crystallography coordinates of human DOT1L amino acid Thr139, Val144, Val169, Phe239, Val240, Asn241, Val267, Ser268, or Ser269, or combination thereof, for example, the crystallography coordinates are within about a root mean square deviation of not more than about 3 Å (e.g., not more than about 2.5 Å, not more than about 2 Å, or not more than about 1.5 Å) from the backbone atoms of the amino acid according to Table S1 or S2.

For example, the SAM binding pocket or the hydrophobic pocket domain of human DOT1L is characterized by the ligand plot as shown in any of FIGS. 6-9.

For example, the binding affinity (K_i) of the compound to human DOT1L is not greater than 50 μM, not greater than 10 μM, not greater than 5 μM, not greater than 2.5 μM, or not greater than 1 μM.

The term “associating with” refers to a condition of proximity between a chemical entity or compound, or portions thereof, and a binding pocket or binding site on a protein. The association may be non-covalent, wherein the juxtaposition is energetically favored by hydrogen bonding, hydrophobic, van der Waals or electrostatic interactions, or it may be covalent.

The term “binding pocket” or “binding site” of DOT1L refers to a region of DOT1L or a molecular complex comprising DOT1L that, as a result of the primary amino acid sequence of human DOT1L and/or its three-dimensional shape, favorably associates with another chemical entity. The term “pocket” includes, but is not limited to, a cleft, channel or site. The shape of a binding pocket may be largely pre-formed before binding of a chemical entity, may be formed simultaneously with binding of a chemical entity, or may be formed by the binding of another chemical entity to a different binding pocket of the molecule, which in turn induces a change in shape of the binding pocket.

The term “chemical entity” refers to chemical compounds, complexes of at least two chemical compounds, and fragments of such compounds or complexes. The chemical entity can be, for example, a ligand, substrate, nucleotide triphosphate, nucleotide diphosphate, phosphate, nucleotide, agonist, antagonist, inhibitor, antibody, peptide, protein or drug. In one embodiment, the chemical entity is an inhibitor or substrate for the active site.

The term “DOT1L complex” or the like refers to a molecular complex formed by associating the DOT1L protein with a chemical entity, for example, a ligand, a substrate, nucleotide triphosphate, nucleotide diphosphate, phosphate, an agonist or antagonist, inhibitor, antibody, drug or compound.

As used herein, the term “inhibitor complex” or the like refers to an association of two or more chemical compounds which can inhibit DOT1L activity. For example, an inhibitor complex is a complex of a compound having the adenosine-like moiety and another compound having a R₉ group and the complex does not have the linker group T.

The term “root mean square deviation” means the square root of the arithmetic mean of the squares of the deviations from the mean.

As used herein, the term “hydrogen bond” refers to two hydrophilic atoms (either O or N), which share a hydrogen that is covalently bonded to only one atom, while interacting with the other.

As used herein, the term “hydrophobic interaction” refers to interactions made by two hydrophobic residues or atoms (such as carbon).

As used herein, the term “crystallography coordinates” or “structure coordinates” refers to mathematical coordinates that describe the positions of atoms in crystals of hDOT1L in Protein Data Bank (PDB) format, including X, Y, Z and B, for each atom. The diffraction data obtained from the crystals are used to calculate an electron density map of the repeating unit of the crystal. The electron density maps may be used to establish the positions (i.e. coordinates X, Y and Z) of the individual atoms within the crystal.

As used herein, the term “ligand” refers to any molecule, or chemical entity, which binds with or to DOT1L, a subunit of DOT1L, a domain of DOT1L, a target structural motif of DOT1L, or a fragment of DOT1L. Thus, ligands include, but are not limited to, modulators of DOT1L activity such as small molecule inhibitors, small molecule agonists, and small molecule inverse agonists, for example.

As used herein, the term “small molecule inhibitor” refers to ligands useful in the present invention having the ability to modulate a measurable amount of DOT1L activity. For example, a small molecule inhibitor has MW of less than 10,000 Daltons, and preferably less than 5,000 Daltons.

As used herein, the term “homolog” refers to the DOT1L protein molecule or the nucleic acid molecule which encodes the protein, or a functional domain from said protein from a first source having at least about 70% or 75% sequence identity, or at least about 80% sequence identity, or more preferably at least about 85% sequence identity, or even more preferably at least about 90% sequence identity, and most preferably at least about 95%, 97% or 99% sequence identity, with the amino acid sequence of the protein, the encoding nucleic acid molecule, or any functional domain thereof, from a second source. The second source may be a version of the molecule from the first source that has been genetically altered by any available means to change the primary amino acid or nucleotide sequence or may be from the same or a different species than that of the first source.

As used herein, the term “active site” refers to regions on DOT1L or a structural motif of DOT1L that are directly involved in the function or activity of human DOT1L.

The term “part of a binding pocket” refers to less than all of the amino acid residues that define the binding pocket. The structure coordinates of amino acid residues that constitute part of a binding pocket may be specific for defining the chemical environment of the binding pocket, or useful in designing fragments of an inhibitor that may interact with those residues.

For example, the portion of amino acid residues may be key residues that play a role in ligand binding, or may be residues that are spatially related and define a three-dimensional compartment of the binding pocket. The amino acid residues may be contiguous or non-contiguous in primary sequence. In one embodiment, part of the binding pocket has at least two amino acid residues, preferably at least three, six, eight, ten, fourteen or fifteen amino acid residues.

In one aspect, a candidate which can be identified or optimized as a DOT1L inhibitor by the method of the invention is a compound of Formula (I) below or a pharmaceutically acceptable salt or ester thereof:

wherein,

Nuc is a nucleoside moiety (e.g., an adenosine-like moiety) or an analog or a derivative thereof,

T is a linker group of a 6-10 carbon atoms, in which one or more carbon atoms are optionally replaced with a heteroatom and T is optionally substituted;

Nuc-T is capable of binding within the SAM binding pocket of human DOT1L which comprises amino acid residues 135-241 of SEQ ID NO: 1; and

R₉ is a group such that R₉ induces a conformational adaptation in human DOT1L, wherein the conformational adaptation is the formation of a hydrophobic pocket domain which comprises amino acid residues 139-312 of SEQ ID NO: 1

The compound of Formula (I) may include one or more of the following features:

For example, R₉ is a group such that R₉ induces a residence time of the compound greater than 20 seconds in a complex formed of the compound and human DOT1L.

For example, R₉ is a group such that R₉ induces a conformational adaptation in human DOT1L, wherein the conformational adaptation is the formation of a hydrophobic pocket domain which is characterized by the crystallography coordinates of human DOT1L amino acids Leu143, Met147, Phe239, and Tyr312, wherein the crystallography coordinates are within about a root mean square deviation of not more than about 2 Å from the backbone atoms of the amino acids according to Table S1 or S2;

For example, Nuc is an adenosine-like moiety.

For example, the adenosine-like moiety can be

which:

A is O or CH₂;

each of G and J, independently, is H, halo, C(O)OH, C(O)O—C₁-C₆ alkyl or OR_a, R_a being H, C₁-C₆ alkyl, C(O)—C₁-C₆ alkyl, or silyl, wherein C(O)O—C₁-C₆ alkyl, C₁-C₆ alkyl or C(O)—C₁-C₆ alkyl is optionally substituted with one or more substituents selected from the group consisting of halo, cyano hydroxyl, carboxyl, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, and C₃-C₈ cycloalkyl;

• • each X independently is N or CR_x, in which R_x is H, halo, hydroxyl, carboxyl, cyano, or R_S1, R_S1 being amino, C₁-C₆ alkoxyl, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and R_S1 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

each of R₁ and R₂, independently is H, halo, hydroxyl, carboxyl, cyano, or R_S2, R_S2 being amino, C₁-C₆ alkoxyl, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, or C₃-C₈ cycloalkyl, and each R_S2 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

R₈ is H, halo or R_S3, R_S3 being C₁-C₆ alkyl, C₂-C₆ alkenyl, or C₂-C₆ alkynyl, and R_S3 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano amino, C₁-C₆ alkoxyl, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, and C₃-C₅ cycloalkyl; and

Q is H, NH₂, NHR_b, NR_bR_c, R_b, ═O, OH, or OR_b, in which each of R_b and R_c independently is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 7-membered heterocycloalkyl, 5 to 10-membered heteroaryl, or -M₁-T₁ in which M₁ is a bond or C₁-C₆ alkyl linker optionally substituted with halo, cyano, hydroxyl or C₁-C₆ alkoxyl and T₁ is C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 10-membered heteroaryl, or R_b and R_c, together with the N atom to which they attach, form 4 to 7-membered heterocycloalkyl having 0 or 1 additional heteroatoms to the N atom optionally substituted with C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, C(O)OH, C(O)O—C₁-C₆ alkyl, OC(O)—C₁-C₆ alkyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and each of R_b, R_c, and T₁ is optionally substituted with one or more substituents selected from the group consisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl.

For example, the adenosine-like moiety is

For example, the residence time of the compound in the DOT1L-compound complex is ≧50 seconds, ≧100 seconds, ≧2 minutes, ≧10 minutes, ≧30 minutes, ≧1 hr, ≧5 hr, ≧10 hr, ≧20 hr, or ≧30 hr.

For example, the compound has a residence time in the DOT1L-compound complex not shorter than that of Compound D16.

For example, the compound has a residence time in the DOT1L-compound complex not shorter than that of Compound A2.

For example, the SAM binding pocket of human DOT1L is characterized by the crystallography coordinates of human DOT1L amino acids Asp161, Gly163, Glu 186, Asp222, and Asn241. For example, the crystallography coordinates are within about a root mean square deviation of not more than about 3 Å (e.g., not more than about 2.5 Å, not more than about 2 Å, or not more than about 1.5 Å) from the backbone atoms of the amino acids according to Table S1 or S2.

For example, the SAM binding pocket of human DOT1L is characterized by the crystallography coordinates of human DOT1L amino acids Val135, Thr139, Asp161, Gly163, Gln168, Glu 186, Asp222, and Asn241. For example, the crystallography coordinates are within about a root mean square deviation of not more than about 3 Å (e.g., not more than about 2.5 Å, not more than about 2 Å, or not more than about 1.5 Å) from the backbone atoms of the amino acids according to Table S1 or S2. The SAM binding pocket of human DOT1L is further characterized by the crystallography coordinates of human DOT1L amino acid Phe223. For example, the crystallography coordinates are within about a root mean square deviation of not more than about 3 Å (e.g., not more than about 2.5 Å, not more than about 2 Å, or not more than about 1.5 Å) from the backbone atoms of the amino acid according to Table S1 or S2.

For example, the hydrophobic pocket domain of human DOT1L is characterized by the crystallography coordinates of human DOT1L amino acids Leu143, Met147, Phe239, and Tyr 312. For example, the crystallography coordinates are within about a root mean square deviation of not more than about 3 Å (e.g., not more than about 2.5 Å, not more than about 2 Å, or not more than about 1.5 Å) from the backbone atoms of the amino acids according to Table S1 or S2. The hydrophobic pocket domain of human DOT1L is further characterized by the crystallography coordinates of human DOT1L amino acid Thr139, Val144, Val169, Phe239, Val240, Asn241, Val267, Ser268, or Ser269, or combination thereof, for example, the crystallography coordinates are within about a root mean square deviation of not more than about 3 Å (e.g., not more than about 2.5 Å, not more than about 2 Å, or not more than about 1.5 Å) from the backbone atoms of the amino acid according to Table S1 or S2.

For example, the SAM binding pocket or the hydrophobic pocket domain of human DOT1L is characterized by the ligand plot as shown in any of FIGS. 6-9.

For example, the binding affinity (K_i) of the compound to human DOT1L is not greater than 50 μM, not greater than 10 μM, not greater than 5 μM, not greater than 2.5 μM, or not greater than 1 μM.

For example, in Formula (I), R₉ comprises C₆-C₁₀ aryl or 5 to 10-membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of unsubstituted or substituted t-butyl, CF₃, cyclohexyl, C₆-C₁₀ aryl, and 5 to 10-membered heteroaryl.

For example, in Formula (I), R₉ is selected from the group consisting of

For example, the compound is of Formula (II):

wherein,

A is O or CH₂;

each of G and J, independently, is H, halo, C(O)OH, C(O)O—C₁-C₆ alkyl or OR_a, R_a being H, C₁-C₆ alkyl, C(O)—C₁-C₆ alkyl, or silyl, wherein C(O)O—C₁-C₆ alkyl, C₁-C₆ alkyl or C(O)—C₁-C₆ alkyl is optionally substituted with one or more substituents selected from the group consisting of halo, cyano hydroxyl, carboxyl, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, and C₃-C₈ cycloalkyl;

each X independently is N or CR_x, in which R_x is H, halo, hydroxyl, carboxyl, cyano, or R_S1, R_S1 being amino, C₁-C₆ alkoxyl, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and R_S1 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

each of R₁ and R₂, independently is H, halo, hydroxyl, carboxyl, cyano, or R_S2, R_S2 being amino, C₁-C₆ alkoxyl, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, or C₃-C₈ cycloalkyl, and each R_S2 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

R₈ is H, halo or R_S3, R_S3 being C₁-C₆ alkyl, C₂-C₆ alkenyl, or C₂-C₆ alkynyl, and R_S3 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano amino, C₁-C₆ alkoxyl, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, and C₃-C₅ cycloalkyl; and

Q is H, NH₂, NHR_b, NR_bR_c, R_b, ═O, OH, or OR_b, in which each of R_b and R_c independently is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 7-membered heterocycloalkyl, 5 to 10-membered heteroaryl, or -M₁-T₁ in which M₁ is a bond or C₁-C₆ alkyl linker optionally substituted with halo, cyano, hydroxyl or C₁-C₆ alkoxyl and T₁ is C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 10-membered heteroaryl, or R_b and R_c, together with the N atom to which they attach, form 4 to 7-membered heterocycloalkyl having 0 or 1 additional heteroatoms to the N atom optionally substituted with C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, C(O)OH, C(O)O—C₁-C₆ alkyl, OC(O)—C₁-C₆ alkyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and each of R_b, R_c, and T₁ is optionally substituted with one or more substituents selected from the group consisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl.

In Formula (I) or (II), T is —CH₂-L₁-L₂-L₃-, with L₃ connected to R₉, wherein:

L₁ is N(Y), S, SO, or SO₂;

L₂ is CO or absent when L₁ is N(Y), or L₂ is absent when L₁ is S, SO, or SO₂, in which Y is H, R_d, SO₂R_d, or COR_d when L₂ is absent, or Y is H or R_d when L₂ is CO, R_d being C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and R_d being optionally substituted with one or more substituents selected from the group consisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, carboxyl, cyano, C₁-C₆ alkoxyl, C₁-C₆ alkylsulfonyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 8-membered heterocycloalkyl, 5 to 6-membered heteroaryl, OR_d′, OCOR_d′, and N(R_d′)₂, and with C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl further optionally substituted with C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, C(O)OH, C(O)O—C₁-C₆ alkyl, OC(O)—C₁-C₆ alkyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl; each R_d′ independently being H, C₁-C₆ alkyl, silyl, C₁-C₆ alkyl-C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 5 to 6-membered heteroaryl, aralkyl, or heteroaralkyl;

L₃ is —(CR₄R₅)_n(CR₆R₇)_m— or —(CR₄R₅)_n-unsubstituted or substituted C₃-C₈ cycloalkyl-(CR₆R₇)_m—, with (CR₆R₇)_m connected to R₉;

each of R₄, R₅, R₆, and R₇, independently, is H, halo, hydroxyl, carboxyl, cyano, or R_S2, R_S2 being amino, C₁-C₆ alkoxyl, C₁-C₆ alkyl, C₂-C₆ alkenyl, or C₂-C₆ alkynyl, and each R_S2 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl; or two geminal R₄ and R₅ or two geminal R₆ and R₇ taken together are ethylene, propylene or butylene;

m is 0, 1, or 2; and

n is 0, 1, or 2.

For example, in Formula (I) or (II), R₉ is

in which:

each of R_e, R_f, R_g, and R_h, independently is -M₂-T₂, in which M₂ is a bond, SO₂, SO, S, CO, CO₂, O, O—C₁-C₄ alkyl linker, C₁-C₄ alkyl linker, NH, or N(R_t), R_t being C₁-C₆ alkyl, and T₂ is H, halo, or R_S4, R_S4 being C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 8-membered heterocycloalkyl, or 5 to 10-membered heteroaryl, and each of O—C₁-C₄ alkyl linker, C₁-C₄ alkyl linker, R_t, and R_S4 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl, R_i is H or C₁-C₆ alkyl optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl,

D is O, NR_j, or CR_jR_k, each of R_j and R_k independently being H or C₁-C₆ alkyl, or R_j and R_k taken together, with the carbon atom to which they are attached, form a C₃-C₁₀ cycloalkyl ring, and E is -M₃-T₃, M₃ being a bond or C₁-C₆ alkyl linker optionally substituted with halo or cyano, T₃ being C₃-C₁₄ carbocycle or 4 to 14-membered heterocycle, and T₃ being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, thiol, carboxyl, cyano, nitro, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkoxyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxyl, C₁-C₆ alkylthio, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁-C₆ alkylcarbonyl, C₁-C₆ alkoxycarbonyl, oxo, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₄-C₁₂ alkylcycloalkyl, C₆-C₁₀ aryl, C₆-C₁₀ aryloxyl, C₇-C₁₄ alkylaryl, C₆-C₁₀ aminoaryloxyl, C₆-C₁₀ arylthio, 4 to 6-membered heterocycloalkyl optionally substituted with halo, C₁-C₄ alkyl, C₁-C₄ haloalkyl, 5 to 6-membered heteroaryl optionally substituted with halo, C₁-C₄ alkyl, and C₁-C₆ alkyl that is substituted with hydroxy, halo, C₁-C₆ alkoxycarbonyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl optionally further substituted with halo, hydroxyl, or C₁-C₆ alkoxyl.

For example, the compound is of formula (IIIa) or (IIIb):

wherein R₃ is H, halo, hydroxyl, carboxyl, cyano, or R_S2, and q is 0, 1, 2, 3, or 4.

For example, the compound is of formula (IIIa) and R₉ is

For example, the compound is of formula (IIIb) and R₉ is

Compounds that are identified as DOT1L inhibitors by the method described herein can also include those of Formula (IIa) or (IIb)

or a pharmaceutically acceptable salt or ester thereof, wherein:

A is O or CH₂;

each of G and J, independently, is H, halo, C(O)OH, C(O)O—C₁-C₆ alkyl or OR_a, R_a being H, C₁-C₆ alkyl or C(O)—C₁-C₆ alkyl, wherein C(O)O—C₁-C₆ alkyl, C₁-C₆ alkyl or C(O)—C₁-C₆ alkyl is optionally substituted with one or more substituents selected from the group consisting of halo, cyano hydroxyl, carboxyl, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, and C₃-C₈ cycloalkyl;

Q is H, NH₂, NHR_b, NR_bR_c, R_b, ═O, OH, or OR_b, in which each of R_b and R_c independently is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 7-membered heterocycloalkyl, 5 to 10-membered heteroaryl, or -M₁-T₁ in which M₁ is a bond or C₁-C₆ alkyl linker optionally substituted with halo, cyano, hydroxyl or C₁-C₆ alkoxyl and T₁ is C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 10-membered heteroaryl, or R_b and R_c, together with the N atom to which they attach, form 4 to 7-membered heterocycloalkyl having 0 or 1 additional heteroatoms to the N atom optionally substituted with C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, C(O)OH, C(O)O—C₁-C₆ alkyl, OC(O)—C₁-C₆ alkyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and each of R_b, R_c, and T₁ is optionally substituted with one or more substituents selected from the group consisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

X is N or CR_x, in which R_x is H, halo, hydroxyl, carboxyl, cyano, or R_S1, R_S1 being amino, C₁-C₆ alkoxyl, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and R_S1 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

L₁ is N(Y), S, SO, or SO₂;

L₂ is CO or absent when L₁ is N(Y) or L₂ is absent when L₁ is S, SO, or SO₂, in which Y is H, R_d, SO₂R_d, or COR_d when L₂ is absent, or Y is H or R_d when L₂ is CO, R_d being C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and R_d being optionally substituted with one or more substituents selected from the group consisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, C₁-C₆ alkylsulfonyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl and with C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl further optionally substituted with C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, C(O)OH, C(O)O—C₁-C₆ alkyl, OC(O)—C₁-C₆ alkyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl;

each of R₁, R₂, R₃, R₄, R₅, R₆, and R₇, independently, is H, halo, hydroxyl, carboxyl, cyano, R_S2, R_S2 being amino, C₁-C₆ alkoxyl, C₁-C₆ alkyl, C₂-C₆ alkenyl, or C₂-C₆ alkynyl, and each R_S2 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

R₈ is H, halo or R_S3, R_S3 being C₁-C₆ alkyl, C₂-C₆ alkenyl, or C₂-C₆ alkynyl, and R_S3 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano amino, C₁-C₆ alkoxyl, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, and C₃-C₅ cycloalkyl;

R₉ is

in which each of R_e, R_f, R_g, and R_h, independently is -M₂-T₂, in which M₂ is a bond, SO₂, SO, S, CO, CO₂, O, O—C₁-C₄ alkyl linker, C₁-C₄ alkyl linker, NH, or N(R_t), R_t being C₁-C₆ alkyl, and T₂ is H, halo, or R_S4, R_S4 being C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 8-membered heterocycloalkyl, or 5 to 10-membered heteroaryl, and each of O—C₁-C₄ alkyl linker, C₁-C₄ alkyl linker, R_t, and R_S4 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl, R_i is H or C₁-C₆ alkyl optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl, D is O, NR_j, or CR_jR_k, each of R_j and R_k independently being H or C₁-C₆ alkyl, or R_j and R_k taken together, with the carbon atom to which they are attached, form a C₃-C₁₀ cycloalkyl ring, and E is -M₃-T₃, M₃ being a bond or C₁-C₆ alkyl linker optionally substituted with halo or cyano, T₃ being C₃-C₁₀ cycloalkyl, C₆-C₁₀ aryl, 5 to 10-membered heteroaryl, or 4 to 10-membered heterocycloalkyl, and T₃ being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, thiol, carboxyl, cyano, nitro, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkoxyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxyl, C₁-C₆ alkylthio, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁-C₆ alkylcarbonyl, C₁-C₆ alkoxycarbonyl, oxo, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₄-C₁₂ alkylcycloalkyl, C₆-C₁₀ aryl, C₆-C₁₀ aryloxyl, C₇-C₁₄ alkylaryl, C₆-C₁₀ aminoaryloxyl, C₆-C₁₀ arylthio, 4 to 6-membered heterocycloalkyl optionally substituted with halo, C₁-C₄ alkyl, C₁-C₄ haloalkyl, 5 to 6-membered heteroaryl optionally substituted with halo, C₁-C₄ alkyl, and C₁-C₆ alkyl that is substituted with hydroxy, halo, C₁-C₆ alkoxycarbonyl, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl optionally further substituted with halo, hydroxyl, or C₁-C₆ alkoxyl;

q is 0, 1, 2, 3, or 4;

m is 0, 1, or 2; and

n is 0, 1, or 2.

For example, the sum of m and n is at least 1.

For example, m is 1 or 2 and n is 0.

For example, m is 2 and n is 0

For example, A is CH₂.

For example, A is O.

For example, L₁ is N(Y).

For example, L₁ is SO or SO₂.

For example, Y is R_d.

For example, R_d is C₁-C₆ alkyl.

For example, L₂ is absent.

For example, each of G and J independently is OR_a.

For example, R_a is H.

For example, R₉ is

For example, R₉ is

For example, at least one of R_e, R_f, R_g, and R_h is halo (such as F, Cl, and Br), C₁-C₆ alkoxyl optionally substituted with one or more halo (such as OCH₃, OCH₂CH₃, O-iPr, and OCF₃), C₁-C₆ alkylsulfonyl optionally substituted with one or more halo (such as SO₂CF₃), or C₁-C₆ alkyl optionally substituted with one or more halo (such as CH₃, i-propyl, n-butyl, and CF₃).

For example, R_i is H or C₁-C₆ alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, s-pentyl and n-hexyl).

For example,

is unsubstituted benzimidazolyl or one of the following groups:

For example, R₉ is

For example, D is O.

For example, D is NR_j.

For example, R_j is H.

For example, D is CR_jR_k.

For example, each of R_j and R_k is H.

For example, E is -M₃-T₃, in which M₃ is a bond or C₁-C₃ alkyl linker, T₃ is phenyl, naphthyl, thienyl, cyclopropyl, or cyclohexyl, and T₃ is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, thiol, carboxyl, cyano, nitro, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkoxyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxyl, C₁-C₆ alkylthio, C₁-C₆ alkylsulfonyl, C₁-C₆ alkylcarbonyl, C₁-C₆ alkoxycarbonyl, oxo, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₄-C₁₂ alkylcycloalkyl, C₆-C₁₀ aryl, C₆-C₁₀ aryloxyl, C₇-C₁₄ alkylaryl, C₆-C₁₀ aminoaryloxyl, C₆-C₁₀ arylthio, 4 to 6-membered heterocycloalkyl optionally substituted with C₁-C₄ alkyl, 5 to 6-membered heteroaryl optionally substituted with C₁-C₄ alkyl, and C₁-C₆ alkyl that is substituted with hydroxy, C₁-C₆ alkoxycarbonyl, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl.

For example, T₃ is phenyl optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, nitro, C₁-C₆ alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, s-pentyl and n-hexyl), C₁-C₆ alkoxyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxyl, C₁-C₆ alkylsulfonyl, C₆-C₁₀ aryl (e.g., phenyl or naphthyl), and C₆-C₁₀ aryloxyl, and C₇-C₁₄ alkylaryl.

For example, E is

For example, X is N.

For example, X is CRY.

For example, X is CH.

For example, Q is NH₂ or NHR_b, in which R_b is -M₁-T₁, M₁ being a bond or C₁-C₆ alkyl linker and T being C₃-C₅ cycloalkyl.

For example, Q is H.

For example, R₁, R₂, R₃, R₄, R₅, R₆, R₇, and R₈ are each H.

For example, when R₈ is halo and is attached to the same carbon atom as J, then J is not hydroxyl.

For example, when R₈ is halo and is attached to the same carbon atom as G, then G is not hydroxyl.

For example, T₂ is not halo when M₂ is SO₂, SO, S, CO or O.

For example, T₂ is a 4-8 membered heterocycloalkyl which is bound to M₂ via a heteroatom.

For example, T₂ is a 4-8 membered heterocycloalkyl which is bound to M₂ via a N atom.

For example, T₂ is a 4-8 membered heterocycloalkyl which is bound to M₂ via a C atom.

Compounds that are identified as DOT1L inhibitors by the method described herein can also include those of Formula (IIc) or (IId):

or a pharmaceutically acceptable salt or ester thereof, wherein the variables are defined herein as for Formula (IIa) or (IIb).

The compound of Formula (II) include those of Formula (IIIa), or (IIIb):

or a pharmaceutically acceptable salt or ester thereof, wherein:

A is O or CH₂;

Q is H, NH₂, NHR_b, NR_bR_c, R_b, ═O, OH, or OR_b, in which each of R_b and R_c independently is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 7-membered heterocycloalkyl, 5 to 10-membered heteroaryl, or -M₁-T₁ in which M₁ is a bond or C₁-C₆ alkyl linker optionally substituted with halo, cyano, hydroxyl, or C₁-C₆ alkoxyl and T₁ is C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 10-membered heteroaryl, or R_b and R_c, together with the N atom to which they attach, form 4 to 7-membered heterocycloalkyl having 0 or 1 additional heteroatoms to the N atom optionally substituted with C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, C(O)OH, C(O)O—C₁-C₆ alkyl, OC(O)—C₁-C₆ alkyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and each of R_b, R_c, and T1 is optionally substituted with one or more substituents selected from the group consisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

X is N or CR_x, in which R_x is H, halo, hydroxyl, carboxyl, cyano, or R_S1, R_S1 being amino, C₁-C₆ alkoxyl, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and R_S1 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

L₁ is N(Y), S, SO, or SO₂;

L₂ is CO or absent when L₁ is N(Y) or L₂ is absent when L₁ is S, SO, or SO₂, in which Y is H, R_d, SO₂R_d, or COR_d when L₂ is absent, or Y is H or R_d when L₂ is CO, R_d being C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and R_d being optionally substituted with one or more substituents selected from the group consisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, C₁-C₆ alkylsulfonyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl and with C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl further optionally substituted with C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, C(O)OH, C(O)O—C₁-C₆ alkyl, OC(O)—C₁-C₆ alkyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl;

each of R₁, R₂, R₃, R₄, R₅, R₆, and R₇, independently, is H, halo, hydroxyl, carboxyl, cyano, R_S2, R_S2 being amino, C₁-C₆ alkoxyl, C₁-C₆ alkyl, C₂-C₆ alkenyl, or C₂-C₆ alkynyl, and each R_S2 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

R₈ is H, halo or R_S3, R_S3 being C₁-C₆ alkyl, C₂-C₆ alkenyl, or C₂-C₆ alkynyl, and R_S3 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano amino, C₁-C₆ alkoxyl, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, and C₃-C₈ cycloalkyl;

R₉ is

in which each of R_e, R_f, R_g, and R_h, independently is -M₂-T₂, in which M₂ is a bond, SO₂, SO, S, CO, CO₂, O, O—C₁-C₄ alkyl linker, C₁-C₄ alkyl linker, NH, or N(R_t), R_t being C₁-C₆ alkyl, and T₂ is H, halo, or R_S4, R_S4 being C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 8-membered heterocycloalkyl, or 5 to 10-membered heteroaryl, and each of O—C₁-C₄ alkyl linker, C₁-C₄ alkyl linker, R_t, and R_S4 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl, R_i is H or C₁-C₆ alkyl optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl, D is O, NR_j, or CR_jR_k, each of R_j and R_k independently being H or C₁-C₆ alkyl, or R_j and R_k taken together, with the carbon atom to which they are attached, form a C₃-C₁₀ cycloalkyl ring, and E is -M₃-T₃, M₃ being a bond or C₁-C₆ alkyl linker optionally substituted with halo or cyano, T₃ being C₃-C₁₀ cycloalkyl, C₆-C₁₀ aryl, 5 to 10-membered heteroaryl, or 4 to 10-membered heterocycloalkyl, and T₃ being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, thiol, carboxyl, cyano, nitro, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkoxyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxyl, C₁-C₆ alkylthio, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁-C₆ alkylcarbonyl, C₁-C₆ alkoxycarbonyl, oxo, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₄-C₁₂ alkylcycloalkyl, C₆-C₁₀ aryl, C₆-C₁₀ aryloxyl, C₇-C₁₄ alkylaryl, C₆-C₁₀ aminoaryloxyl, C₆-C₁₀ arylthio, 4 to 6-membered heterocycloalkyl optionally substituted with halo, C₁-C₄ alkyl, C₁-C₄ haloalkyl, 5 to 6-membered heteroaryl optionally substituted with halo, C₁-C₄ alkyl, and C₁-C₆ alkyl that is substituted with hydroxy, halo, C₁-C₆ alkoxycarbonyl, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl optionally further substituted with halo, hydroxyl, or C₁-C₆ alkoxyl;

q is 0, 1, 2, 3, or 4;

m is 0, 1, or 2; and

n is 0, 1, or 2.

For example, the sum of m and n is at least 1.

For example, m is 1 or 2 and n is 0.

For example, m is 2 and n is 0

For example, A is CH₂.

For example, A is O.

For example, L₁ is N(Y).

For example, L₁ is SO or SO₂.

For example, Y is R_d.

For example, R_d is C₁-C₆ alkyl.

For example, L₂ is absent.

For example, R₉ is

For example, R₉ is

For example, at least one of R_e, R_f, R_g, and R_h is halo (such as F, Cl, and Br), C₁-C₆ alkoxyl optionally substituted with one or more halo (such as OCH₃, OCH₂CH₃, O-iPr, and OCF₃), C₁-C₆ alkylsulfonyl optionally substituted with one or more halo (such as SO₂CF₃), or C₁-C₆ alkyl optionally substituted with one or more halo (such as CH₃, i-propyl, n-butyl, and CF₃).

For example, R_i is H or C₁-C₆ alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, s-pentyl or n-hexyl).

For example,

is unsubstituted benzimidazolyl or one of the following groups:

For example, R₉ is

For example, D is O.

For example, D is NR_j.

For example, R_j is H.

For example, D is CR_jR_k.

For example, each of R_j and R_k is H.

For example, E is -M₃-T₃, in which M₃ is a bond or C₁-C₃ alkyl linker, T₃ is phenyl, naphthyl, thienyl, cyclopropyl, or cyclohexyl, and T₃ is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, thiol, carboxyl, cyano, nitro, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkoxyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxyl, C₁-C₆ alkylthio, C₁-C₆ alkylsulfonyl, C₁-C₆ alkylcarbonyl, C₁-C₆ alkoxycarbonyl, oxo, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₄-C₁₂ alkylcycloalkyl, C₆-C₁₀ aryl, C₆-C₁₀ aryloxyl, C₇-C₁₄ alkylaryl, C₆-C₁₀ aminoaryloxyl, C₆-C₁₀ arylthio, 4 to 6-membered heterocycloalkyl optionally substituted with C₁-C₄ alkyl, 5 to 6-membered heteroaryl optionally substituted with C₁-C₄ alkyl, and C₁-C₆ alkyl that is substituted with hydroxy, C₁-C₆ alkoxycarbonyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl.

For example, T₃ is phenyl optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, nitro, C₁-C₆ alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, s-pentyl and n-hexyl), C1-C₆ alkoxyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxyl, C₁-C₆ alkylsulfonyl, C₆-C₁₀ aryl (e.g., phenyl or naphthyl), and C₆-C₁₀ aryloxyl, and C₇-C₁₄ alkylaryl.

For example, E is

For example, X is N.

For example, X is CR_x.

For example, X is CH.

For example, Q is NH₂ or NHR_b, in which R_b is -M₁-T₁, M₁ being a bond or C₁-C₆ alkyl linker and T₁ being C₃-C₅ cycloalkyl.

For example, Q is H.

For example, R₁, R₂, R₃, R₄, R₅, R₆, R₇, and R₈ are each H.

For example, when R₈ is halo and is attached to the same carbon atom as J, then J is not hydroxyl.

For example, when R₈ is halo and is attached to the same carbon atom as G, then G is not hydroxyl.

For example, T₂ is not halo when M₂ is SO₂, SO, S, CO or O.

For example, T₂ is a 4-8 membered heterocycloalkyl which is bound to M₂ via a heteroatom.

For example, T₂ is a 4-8 membered heterocycloalkyl which is bound to M₂ via a N atom.

For example, T₂ is a 4-8 membered heterocycloalkyl which is bound to M₂ via a C atom.

The present invention provides the compounds of Formula (IVa), (IVb), (IVd), or (IVe):

or a pharmaceutically acceptable salt or ester thereof, wherein:

A is O or CH₂;

each of G and J, independently, is H, halo, C(O)OH, C(O)O—C₁-C₆ alkyl or OR_a, R_a being H, C₁-C₆ alkyl or C(O)—C₁-C₆ alkyl, wherein C(O)O—C₁-C₆ alkyl, C₁-C₆ alkyl or C(O)—C₁-C₆ alkyl is optionally substituted with one or more substituents selected from the group consisting of halo, cyano hydroxyl, carboxyl, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, and C₃-C₅ cycloalkyl;

Q is H, NH₂, NHR_b, NR_bR_c, R_b, ═O, OH, or OR_b, in which each of R_b and R_c independently is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 7-membered heterocycloalkyl, 5 to 10-membered heteroaryl, or -M₁-T₁ in which M₁ is a bond or C₁-C₆ alkyl linker optionally substituted with halo, cyano, hydroxyl or C₁-C₆ alkoxyl and T₁ is C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 10-membered heteroaryl, or R_b and R_c, together with the N atom to which they attach, form 4 to 7-membered heterocycloalkyl having 0 or 1 additional heteroatoms to the N atom optionally substituted with C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, C(O)OH, C(O)O—C₁-C₆ alkyl, OC(O)—C₁-C₆ alkyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and each of R_b, R_c, and T₁ is optionally substituted with one or more substituents selected from the group consisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

X is N or CR_x, in which R_x is H, halo, hydroxyl, carboxyl, cyano, or R_S1, R_S1 being amino, C₁-C₆ alkoxyl, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and R_S1 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

L₁ is N(Y), S, SO, or SO₂;

L₂ is CO or absent when L₁ is N(Y) or L₂ is absent when L₁ is S, SO, or SO₂, in which Y is H, R_d, SO₂R_d, or COR_d when L₂ is absent, or Y is H or R_d when L₂ is CO, R_d being C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and R_d being optionally substituted with one or more substituents selected from the group consisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, C₁-C₆ alkylsulfonyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl and with C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl further optionally substituted with C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, C(O)OH, C(O)O—C₁-C₆ alkyl, OC(O)—C₁-C₆ alkyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl;

each of R₁, R₂, R₃, R₄, R₅, R₆, and R₇, independently, is H, halo, hydroxyl, carboxyl, cyano, R_S2, R_S2 being amino, C₁-C₆ alkoxyl, C₁-C₆ alkyl, C₂-C₆ alkenyl, or C₂-C₆ alkynyl, and each R_S2 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

R₈ is H, halo or R_S3, R_S3 being C₁-C₆ alkyl, C₂-C₆ alkenyl, or C₂-C₆ alkynyl, and R_S3 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano amino, C₁-C₆ alkoxyl, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, and C₃-C₈ cycloalkyl;

each of R_e, R_f, R_g, and R_h, independently is -M₂-T₂, in which M₂ is a bond, SO₂, SO, S, CO, CO₂, O, O—C₁-C₄ alkyl linker, C₁-C₄ alkyl linker, NH, or N(R_t), R_t being C₁-C₆ alkyl, and T₂ is H, halo, or R_S4, R_S4 being C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 8-membered heterocycloalkyl, or 5 to 10-membered heteroaryl, and each of O—C₁-C₄ alkyl linker, C₁-C₄ alkyl linker, R_t, and R_S4 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl,

R_i is H or C₁-C₆ alkyl optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

q is 0, 1, 2, 3, or 4;

m is 0, 1, or 2; and

n is 0, 1, or 2.

For example, the sum of m and n is at least 1.

For example, m is 1 or 2 and n is 0.

For example, m is 2 and n is 0

For example, A is CH₂.

For example, A is O.

For example, L₁ is N(Y).

For example, L₁ is SO or SO₂.

For example, Y is R_d.

For example, R_d is C₁-C₆ alkyl.

For example, L₂ is absent.

For example, each of G and J independently is OR_a.

For example, R_a is H.

For example, at least one of R_e, R_f, R_g, and R_h is halo (such as F, Cl, and Br), C₁-C₆ alkoxyl optionally substituted with one or more halo (such as OCH₃, OCH₂CH₃, O-iPr, and OCF₃), C₁-C₆ alkylsulfonyl optionally substituted with one or more halo (such as SO₂CF₃), or C₁-C₆ alkyl optionally substituted with one or more halo (such as CH₃, i-propyl, n-butyl, and CF₃).

For example, R_i is H or C₁-C₆ alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, s-pentyl and n-hexyl).

For example,

is unsubstituted benzimidazolyl or one of the following groups:

For example, X is N.

For example, X is CR_x.

For example, X is CH.

For example, Q is NH₂ or NHR_b, in which R_b is -M₁-T₁, M₁ being a bond or C₁-C₆ alkyl linker and T₁ being C₃-C₈ cycloalkyl.

For example, Q is H.

For example, R₁, R₂, R₃, R₄, R₅, R₆, R₇, and R₈ are each H.

For example, when R₈ is halo and is attached to the same carbon atom as J, then J is not hydroxyl.

For example, when R₈ is halo and is attached to the same carbon atom as G, then G is not hydroxyl.

For example, T₂ is not halo when M₂ is SO₂, SO, S, CO or O.

For example, T₂ is a 4-8 membered heterocycloalkyl which is bound to M₂ via a heteroatom.

For example, T₂ is a 4-8 membered heterocycloalkyl which is bound to M₂ via a N atom.

For example, T₂ is a 4-8 membered heterocycloalkyl which is bound to M₂ via a C atom.

The present invention provides the compounds of Formula (IVc) or (IVf):

or a pharmaceutically acceptable salt or ester thereof, wherein:

A is O or CH₂;

each of G and J, independently, is H, halo, C(O)OH, C(O)O—C₁-C₆ alkyl or OR_a, R_a being H, C₁-C₆ alkyl or C(O)—C₁-C₆ alkyl, wherein C(O)O—C₁-C₆ alkyl, C₁-C₆ alkyl or C(O)—C₁-C₆ alkyl is optionally substituted with one or more substituents selected from the group consisting of halo, cyano hydroxyl, carboxyl, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, and C₃-C₈ cycloalkyl;

Q is H, NH₂, NHR_b, NR_bR_c, R_b, ═O, OH, or OR_b, in which each of R_b and R_c independently is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 7-membered heterocycloalkyl, 5 to 10-membered heteroaryl, or -M₁-T₁ in which M₁ is a bond or C₁-C₆ alkyl linker optionally substituted with halo, cyano, hydroxyl or C₁-C₆ alkoxyl and T₁ is C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 10-membered heteroaryl, or R_b and R_c, together with the N atom to which they attach, form 4 to 7-membered heterocycloalkyl having 0 or 1 additional heteroatoms to the N atom optionally substituted with C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, C(O)OH, C(O)O—C₁-C₆ alkyl, OC(O)—C₁-C₆ alkyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and each of R_b, R_c, and T₁ is optionally substituted with one or more substituents selected from the group consisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

X is N or CR_x, in which R_x is H, halo, hydroxyl, carboxyl, cyano, or R_S1, R_S1 being amino, C₁-C₆ alkoxyl, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and R_S1 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

L₁ is N(Y), S, SO, or SO₂;

L₂ is CO or absent when L₁ is N(Y) or L₂ is absent when L₁ is S, SO, or SO₂, in which Y is H, R_d, SO₂R_d, or COR_d when L₂ is absent, or Y is H or R_d when L₂ is CO, R_d being C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and R_d being optionally substituted with one or more substituents selected from the group consisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, C₁-C₆ alkylsulfonyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl and with C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl further optionally substituted with C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, C(O)OH, C(O)O—C₁-C₆ alkyl, OC(O)—C₁-C₆ alkyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl;

each of R₁, R₂, R₃, R₄, R₅, R₆, and R₇, independently, is H, halo, hydroxyl, carboxyl, cyano, R_S2, R_S2 being amino, C1-C₆ alkoxyl, C₁-C₆ alkyl, C₂-C₆ alkenyl, or C₂-C₆ alkynyl, and each R_S2 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;

R₈ is H, halo or R_S3, R_S3 being C₁-C₆ alkyl, C₂-C₆ alkenyl, or C₂-C₆ alkynyl, and R_S3 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano amino, C₁-C₆ alkoxyl, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, and C₃-C₅ cycloalkyl;

D is O, NR_j, or CR_jR_k, each of R_j and R_k independently being H or C₁-C₆ alkyl, or R_j and R_k taken together, with the carbon atom to which they are attached, form a C₃-C₁₀ cycloalkyl ring;

E is -M₃-T₃, M₃ being a bond or C₁-C₆ alkyl linker optionally substituted with halo or cyano, T₃ being C₃-C₁₀ cycloalkyl, C₆-C₁₀ aryl, 5 to 10-membered heteroaryl, or 4 to 10-membered heterocycloalkyl, and T₃ being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, thiol, carboxyl, cyano, nitro, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkoxyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxyl, C₁-C₆ alkylthio, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁-C₆ alkylcarbonyl, C₁-C₆ alkoxycarbonyl, oxo, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₄-C₁₂ alkylcycloalkyl, C₆-C₁₀ aryl, C₆-C₁₀ aryloxyl, C₇-C₁₄ alkylaryl, C₆-C₁₀ aminoaryloxyl, C₆-C₁₀ arylthio, 4 to 6-membered heterocycloalkyl optionally substituted with halo, C₁-C₄ alkyl, C₁-C₄ haloalkyl, 5 to 6-membered heteroaryl optionally substituted with halo, C₁-C₄ alkyl, and C₁-C₆ alkyl that is substituted with hydroxy, halo, C₁-C₆ alkoxycarbonyl, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl optionally further substituted with halo, hydroxyl, or C₁-C₆ alkoxyl;

q is 0, 1, 2, 3, or 4;

m is 0, 1, or 2; and

n is 0, 1, or 2.

For example, the sum of m and n is at least 1.

For example, m is 1 or 2 and n is 0.

For example, m is 2 and n is 0

For example, A is CH₂.

For example, A is O.

For example, L₁ is N(Y).

For example, L₁ is SO or SO₂.

For example, Y is R_d.

For example, R_d is C1-C₆ alkyl.

For example, L₂ is absent.

For example, each of G and J independently is OR_a.

For example, R_a is H.

For example, D is O.

For example, D is NR_j.

For example, R_j is H.

For example, D is CR_jR_k.

For example, each of R_j and R_k is H.

For example, E is -M₃-T₃, in which M₃ is a bond or C₁-C₃ alkyl linker, T₃ is phenyl, naphthyl, thienyl, cyclopropyl, or cyclohexyl, and T₃ is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, thiol, carboxyl, cyano, nitro, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkoxyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxyl, C₁-C₆ alkylthio, C₁-C₆ alkylsulfonyl, C₁-C₆ alkylcarbonyl, C₁-C₆ alkoxycarbonyl, oxo, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₄-C₁₂ alkylcycloalkyl, C₆-C₁₀ aryl, C₆-C₁₀ aryloxyl, C₇-C₁₄ alkylaryl, C₆-C₁₀ aminoaryloxyl, C₆-C₁₀ arylthio, 4 to 6-membered heterocycloalkyl optionally substituted with C₁-C₄ alkyl, 5 to 6-membered heteroaryl optionally substituted with C₁-C₄ alkyl, and C₁-C₆ alkyl that is substituted with hydroxy, C₁-C₆ alkoxycarbonyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl.

For example, T₃ is phenyl optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, nitro, C1-C₆ alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, s-pentyl and n-hexyl), C₁-C₆ alkoxyl, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxyl, C₁-C₆ alkylsulfonyl, C₆-C₁₀ aryl (e.g., phenyl or naphthyl), and C₆-C₁₀ aryloxyl, and C₇-C₁₄ alkylaryl.

For example, E is

For example, X is N.

For example, X is CR_x.

For example, X is CH.

For example, Q is NH₂ or NHR_b, in which R_b is -M₁-T₁, M₁ being a bond or C₁-C₆ alkyl linker and T₁ being C₃-C₈ cycloalkyl.

For example, Q is H.

For example, R₁, R₂, R₃, R₄, R₅, R₆, R₇, and R₈ are each H.

For example, when R₈ is halo and is attached to the same carbon atom as J, then J is not hydroxyl.

For example, when R₈ is halo and is attached to the same carbon atom as G, then G is not hydroxyl.

For example, T₂ is not halo when M₂ is SO₂, SO, S, CO or O.

For example, T₂ is a 4-8 membered heterocycloalkyl which is bound to M₂ via a heteroatom.

For example, T₂ is a 4-8 membered heterocycloalkyl which is bound to M₂ via a N atom.

For example, T₂ is a 4-8 membered heterocycloalkyl which is bound to M₂ via a C atom.

The invention also relates to a compound of Formula (IV) or its N-oxide or a pharmaceutically acceptable salt thereof:

wherein A is O or CH₂;Q is H, NH₂, NHR_b, NR_bR_c, R_b, ═O, OH, or OR_b, in which each of R_b and R_c independently is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 7-membered heterocycloalkyl, 5 to 10-membered heteroaryl, or -M₁-T₁ in which M₁ is a bond or C₁-C₆ alkyl linker optionally substituted with halo, cyano, hydroxyl or C₁-C₆ alkoxyl and T₁ is C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 10-membered heteroaryl, or R_b and R_c, together with the N atom to which they attach, form 4 to 7-membered heterocycloalkyl having 0 or 1 additional heteroatoms to the N atom optionally substituted with C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, C(O)OH, C(O)O—C₁-C₆ alkyl, OC(O)—C₁-C₆ alkyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and each of R_b, R_c, and T₁ is optionally substituted with one or more substituents selected from C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;X is N or CR_x, in which R_x is H, halo, hydroxyl, carboxyl, cyano, or R_S1, R_S1 being amino, C₁-C₆ alkoxyl, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and R_S1 being optionally substituted with one or more substituents selected from halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;Y is H, R_d, SO₂R_d, or COR_d, R_d being C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₅ cycloalkyl, C6-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and R_d being optionally substituted with one or more substituents selected from C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, C₁-C₆ alkylsulfonyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl and with C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl further optionally substituted with C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, halo, hydroxyl, carboxyl, C(O)OH, C(O)O—C₁-C₆ alkyl, OC(O)—C₁-C₆ alkyl, cyano, C1-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl;each of R₁ and R₂ independently, is H, halo, hydroxyl, carboxyl, cyano, R_S2, R_S2 being amino, C1-C₆ alkoxyl, C1-C₆ alkyl, C₂-C₆ alkenyl, or C₂-C₆ alkynyl, and each R_S2 being optionally substituted with one or more substituents selected from halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl;each of R_e, R_f, R_g, and R_h, independently is -M₂-T₂, in which M₂ is a bond, SO₂, SO, S, CO, CO₂, O, O—C₁-C₄ alkyl linker, C₁-C₄ alkyl linker, NH, or N(R_t), R_t being C₁-C₆ alkyl, and T₂ is H, halo, or R_S4, R_S4 being C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 8-membered heterocycloalkyl, or 5 to 10-membered heteroaryl, and each of O—C₁-C₄ alkyl linker, C₁-C₄ alkyl linker, R_t, and R_S4 being optionally substituted with one or more substituents selected from halo, hydroxyl, carboxyl, cyano, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkoxyl, amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, C₃-C₅ cycloalkyl, C₆-C₁₀ aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl, and m is 0, 1, or 2.

For example, A is O. In certain compounds of Formula (IV), A is O and m is 2.

In certain compounds of Formula (IV), X is N.

For example, in certain compounds, Q is NH₂ or NHR_b, in which R_b is -M₁-T₁, M₁ being a bond or C₁-C₆ alkyl linker and T₁ being C₃-C₅ cycloalkyl

For example, in certain compounds of Formula (IV), R₁ and R₂ are each H.

In certain compounds of Formula (IV), Y is R_d. For example, R_d is C₁-C₆ alkyl optionally substituted with C₃-C₈ cycloalkyl or halo. For example, R_d is C₃-C₈ cycloalkyl optionally substituted with C₁-C₆ alkyl or halo.

The invention also relates to a compound of Formula (IV), wherein at least one of R_e, R_f, R_g, and R_h is halo, C₁-C₆ alkoxyl optionally substituted with one or more halo; C₁-C₆ alkylsulfonyl optionally substituted with one or more halo; C₁-C₆ alkyl optionally substituted with one or more substituents selected from CN, halo, C₃-C₅ cycloalkyl, hydroxy, and C₁-C₆ alkoxyl; C₃-C₈ cycloalkyl optionally substituted with one or more C₁-C₆ alkyl or CN; or 4 to 8-membered heterocycloalkyl optionally substituted with one or more substituents selected from CN, halo, hydroxy, C₁-C₆ alkyl and C₁-C₆ alkoxyl. For example, the compound of Formula (IV) has at least one of R_e, R_f, R_g, and R_h selected from F; Cl; Br; CF₃; OCF₃; SO₂CF₃; oxetanyl optionally substituted with one or more substituents selected from CN, halo, hydroxy, C₁-C₆ alkyl and C₁-C₆ alkoxyl; C₃-C₈ cycloalkyl optionally substituted with one or more substituents selected from C₁-C₄ alkyl; and C₁-C₄ alkyl optionally substituted with one or more substituents selected from halo, C₃-C₅ cycloalkyl, hydroxy and C₁-C₆ alkoxyl.

For example, the invention relates to compounds of Formula (IV) where at least one of R_f and R_g is alkyl, optionally substituted with hydroxyl. For example, the invention relates to compounds where at least one of R_f and R_g is t-butyl substituted with hydroxyl.

The invention relates to a compound selected from Tables 1-4. The invention also relates to a salt of a compound selected from Tables 1-4. The invention also relates to an N-oxide of compound selected from Tables 1-4. The invention also relates to a salt of an N-oxide of compound selected from Tables 1-4. For example, the invention relates to a compound selected from Compounds A1-A7, A9-A109, and A111-A140.

Other compounds suitable for the methods of the invention, as well as pharmaceutical compositions and uses thereof, are described in WO2012/075381, WO2012/075492, WO2012/082436, and WO2012/75500, the contents of which are hereby incorporated by reference in their entireties.

The invention also relates to a pharmaceutical composition of a therapeutically effective amount of a compound of any of the Formulae disclosed herein and a pharmaceutically acceptable carrier.

The invention also relates to a pharmaceutical composition of a therapeutically effective amount of a salt of a compound of any of the Formulae disclosed herein and a pharmaceutically acceptable carrier.

The invention also relates to a pharmaceutical composition of a therapeutically effective amount of a hydrate of a compound of any of the Formulae disclosed herein and a pharmaceutically acceptable carrier.

The invention also relates to a pharmaceutical composition of a therapeutically effective amount of a compound selected from Tables 1-4 and a pharmaceutically acceptable carrier. The invention also relates to a pharmaceutical composition of a therapeutically effective amount of a salt of a compound selected from Tables 1-4 and a pharmaceutically acceptable carrier. The invention also relates to a pharmaceutical composition of a therapeutically effective amount of an N-oxide of a compound selected from Tables 1-4 and a pharmaceutically acceptable carrier. The invention also relates to a pharmaceutical composition of a therapeutically effective amount of an N-oxide of salt of a compound selected from Tables 1-4 and a pharmaceutically acceptable carrier. The invention also relates to a pharmaceutical composition of a therapeutically effective amount of a hydrate of a compound selected from Tables 1-4 and a pharmaceutically acceptable carrier.

The present invention provides methods of treating or preventing cancer. The present invention provides methods of treating cancer. The present invention also provides methods of preventing cancer. The method includes administering to a subject in need thereof a therapeutically effective amount of the compound of any of the Formulae disclosed herein. The cancer can be a hematological cancer. Preferably, the cancer is leukemia. More preferably, the cancer is acute myeloid leukemia, acute lymphocytic leukemia or mixed lineage leukemia.

The present invention provides methods of treating or preventing a disease or disorder mediated by translocation of a gene on chromosome 11q23. The present invention provides methods of treating a disease or disorder mediated by translocation of a gene on chromosome 11q23. The present invention also provides methods of preventing a disease or disorder mediated by translocation of a gene on chromosome 11q23. The method includes administering to a subject in need thereof a therapeutically effective amount of the compound of any of the Formulae disclosed herein.

The present invention provides methods of treating or preventing a disease or disorder in which DOT -mediated protein methylation plays a part or a disease or disorder mediated by DOT1-mediated protein methylation. The present invention provides methods of treating a disease or disorder in which DOT1-mediated protein methylation plays a part or a disease or disorder mediated by DOT1-mediated protein methylation. The present invention also provides methods of preventing a disease or disorder in which DOT1-mediated protein methylation plays a part or a disease or disorder mediated by DOT1-mediated protein methylation. The method includes administering to a subject in need thereof a therapeutically effective amount of the compound of any of the Formulae disclosed herein.

The present invention provides methods of inhibiting DOT1L activity in a cell. The method includes contacting the cell with an effective amount of one or more of the compound of any of the Formulae disclosed herein.

Still another aspect of the invention relates to a method of reducing the level of Histone H3 Lysine residue 79 (H3-K79) methylation in a cell. The method includes contacting a cell with a compound of the present invention. Such method can be used to ameliorate any condition which is caused by or potentiated by the activity of DOT1 through H3-K79 methylation.

The present invention relates to use of the compounds disclosed herein in preparation of a medicament for treating or preventing cancer. The use includes a compound of any of the Formulae disclosed herein for administration to a subject in need thereof in a therapeutically effective amount. The cancer can be a hematological cancer. Preferably, the cancer is leukemia. More preferably, the cancer is acute myeloid leukemia, acute lymphocytic leukemia or mixed lineage leukemia.

The present invention provides use of the compounds disclosed herein in preparation of a medicament for treating or preventing a disease or disorder mediated by translocation of a gene on chromosome 11q23. The use includes a compound of any of the Formulae disclosed herein for administration to a subject in need thereof in a therapeutically effective amount.

The present invention provides use of the compounds disclosed herein in preparation of a medicament for treating or preventing a disease or disorder in which DOT1-mediated protein methylation plays a part or a disease or disorder mediated by DOT1-mediated protein methylation. The use includes a compound of any of the Formulae disclosed herein for administration to a subject in need thereof in a therapeutically effective amount.

The present invention provides use of the compounds disclosed herein for inhibiting DOT1L activity in a cell. The use includes contacting the cell with an effective amount of one or more of the compound of any of the Formulae disclosed herein.

Still another aspect of the invention relates to a use of the compounds disclosed herein for reducing the level of Histone H3 Lysine residue 79 (H3-K79) methylation in a cell. The use includes contacting a cell with a compound of the present invention. Such use can ameliorate any condition which is caused by or potentiated by the activity of DOT1 through H3-K79 methylation.

In the formulae presented herein, the variables can be selected from the respective groups of chemical moieties later defined in the detailed description.

In addition, the invention provides methods of synthesizing the foregoing compounds. Following synthesis, a therapeutically effective amount of one or more of the compounds can be formulated with a pharmaceutically acceptable carrier for administration to a mammal, particularly humans, for use in modulating an epigenetic enzyme. In certain embodiments, the compounds of the present invention are useful for treating, preventing, or reducing the risk of cancer or for the manufacture of a medicament for treating, preventing, or reducing the risk of cancer. Accordingly, the compounds or the formulations can be administered, for example, via oral, parenteral, otic, ophthalmic, nasal, or topical routes, to provide an effective amount of the compound to the mammal.

Representative compounds of the present invention include compounds listed in Tables 1-4.

TABLE 1
Cmpd No. Chemical Name
A1       (2R,3S,4R,5R)-2-(((3-(2-(1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)-5-(6-amino-9H-
         purin-9-yl)tetrahydrofuran-3,4-diol
A2       (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A3       (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A4       (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1s,3R)-3-(2-(5-chloro-6-(trifluoromethyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A5       (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-chloro-6-(trifluoromethyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A6       (2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((3-((5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)methyl)cyclobutyl)(methyl)amino)methyl)tetrahydrofuran-3,4-diol
A7       (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((3-(2-(6-chloro-5-(trifluoromethyl)-
         1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A8       1-(3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-
         yl)methyl)(methyl)amino)cyclobutyl)-3-(4-tert-butylphenyl)urea
A9       (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(6-chloro-5-
         (trifluoromethyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A10      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((methyl((1r,3S)-3-(2-(5-
         (trifluoromethyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A11      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((methyl((1s,3R)-3-(2-(5-
         (trifluoromethyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A12      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1s,3R)-3-(2-(6-chloro-5-
         (trifluoromethyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A13      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((methyl(3-(2-(5-(trifluoromethyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A14      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A15      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((isopropyl((3-((5-(trifluoromethyl)-1H-
         benzo[d]imidazol-2-yl)methyl)cyclobutyl)methyl)amino)methyl)cyclopentane-1,2-diol
A16      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((3-(5-chloro-6-(trifluoromethyl)-1H-
         benzo[d]imidazol-2-yl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A17      (1R,2R,4S)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-4-(((3-(2-(5-chloro-6-(trifluoromethyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentanol
A18      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((methyl((3-((5-(trifluoromethyl)-1H-
         benzo[d]imidazol-2-yl)methyl)cyclobutyl)methyl)amino)methyl)cyclopentane-1,2-diol
A19      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)cyclopentane-1,2-diol
A20      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((3-(2-(6-chloro-5-(trifluoromethyl)-
         1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)cyclopentane-1,2-diol
A21      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((3-((6-chloro-5-(trifluoromethyl)-1H-
         benzo[d]imidazol-2-yl)methyl)cyclobutyl)methyl)(isopropyl)amino)methyl)cyclopentane-1,2-diol
A22      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((3-((5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)methyl)cyclobutyl)methyl)(isopropyl)amino)methyl)cyclopentane-1,2-diol
A23      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((3-(2-(5,6-dichloro-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A24      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((methyl(3-(2-(5-(trifluoromethoxy)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A25      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(ethyl)amino)methyl)cyclopentane-1,2-diol
A26      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((3-(2-(5-bromo-1H-benzo[d]imidazol-
         2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A27      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((isopropyl(3-(2-(5-(1-methylcyclobutyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A28      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((isopropyl((1r,3S)-3-(2-(5-(1-methylcyclobutyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A29      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((methyl(3-(2-(5-(1-methylcyclobutyl)-
         1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A30      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((methyl((1r,3S)-3-(2-(5-(1-methylcyclobutyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A31      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((isopropyl((1s,3R)-3-(2-(5-(1-methylcyclobutyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A32      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A33      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((methyl(3-(2-(5-(1-methylcyclobutyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A34      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((methyl((1s,3R)-3-(2-(5-(1-methylcyclobutyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A35      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A36      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((methyl((1r,3S)-3-(2-(5-(1-
         methylcyclobutyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A37      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((methyl((1r,3S)-3-(2-(5-
         (trifluoromethoxy)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A38      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(ethyl)amino)methyl)cyclopentane-1,2-diol
A39      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((methyl((1s,3R)-3-(2-(5-(1-
         methylcyclobutyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A40      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(cyclopropylmethyl)amino)methyl)cyclopentane-1,2-diol
A41      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)cyclopentane-1,2-diol
A42      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(cyclobutylmethyl)amino)methyl)cyclopentane-1,2-diol
A43      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A44      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(cyclopropylmethyl)amino)methyl)cyclopentane-1,2-diol
A45      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isobutyl)amino)methyl)cyclopentane-1,2-diol
A46      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A47      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(5-bromo-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A48      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isobutyl)amino)methyl)cyclopentane-1,2-diol
A49      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(ethyl)amino)methyl)cyclopentane-1,2-diol
A50      (1R,2S,3R,5R)-3-(6-amino-9H-purin-9-yl)-5-(((3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)cyclopentane-1,2-diol
A51      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A52      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(5,6-dichloro-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A53      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isobutyl)amino)methyl)cyclopentane-1,2-diol
A54      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(cyclopropylmethyl)amino)methyl)cyclopentane-1,2-diol
A55      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1s,3R)-3-(2-(5-bromo-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A56      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((isopropyl(3-(2-(5-(trifluoromethoxy)-
         1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A57      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((methyl((1s,3R)-3-(2-(5-
         (trifluoromethoxy)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A58      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1s,3R)-3-(2-(5,6-dichloro-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A59      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(cyclobutylmethyl)amino)methyl)cyclopentane-1,2-diol
A60      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((isopropyl((1r,3S)-3-(2-(5-
         (trifluoromethoxy)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A61      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((isopropyl((1s,3R)-3-(2-(5-
         (trifluoromethoxy)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A62      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((methyl(3-(2-(5-(oxetan-3-yl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)cyclopentane-1,2-diol
A63      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((methyl((1r,3S)-3-(2-(5-(oxetan-3-yl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A64      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((methyl(3-(2-(5-(oxetan-3-yl)-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A65      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((methyl((1s,3R)-3-(2-(5-(oxetan-3-yl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A66      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(2,2,2-trifluoroethyl)amino)methyl)cyclopentane-1,2-diol
A67      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(((3-(2-(5-cyclobutyl-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A68      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(((3-(2-(5-(1-methoxy-2-methylpropan-2-yl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)tetrahydrofuran-3,4-diol
A69      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A70      (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1s,3R)-3-(2-(6-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol
A71      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(methyl)amino)methyl)tetrahydrofuran-3,4-diol
A72      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(methyl)amino)methyl)tetrahydrofuran-3,4-diol
A73      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(ethyl)amino)methyl)tetrahydrofuran-3,4-diol
A74      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(ethyl)amino)methyl)tetrahydrofuran-3,4-diol
A75      (2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A76      (2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((isopropyl((1s,3R)-3-(2-(5-
         (trifluoromethoxy)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A77      (2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(2,2,2-trifluoroethyl)amino)methyl)tetrahydrofuran-3,4-diol
A78      (2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(2,2,2-trifluoroethyl)amino)methyl)tetrahydrofuran-3,4-diol
A79      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(((3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(ethyl)amino)methyl)tetrahydrofuran-3,4-diol
A80      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(2,2,2-trifluoroethyl)amino)methyl)tetrahydrofuran-3,4-diol
A81      (1R,2R,4S)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-4-((((1r,3R)-3-(2-(5-chloro-6-
         (trifluoromethyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentanol
A82      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(((3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(2,2,2-trifluoroethyl)amino)methyl)tetrahydrofuran-3,4-diol
A83      (1R,2R,4S)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-4-(((3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)cyclopentanol
A84      (1R,2R,4S)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-4-(((3-(2-(5-chloro-6-(trifluoromethyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)cyclopentanol
A85      (1R,2R,4S)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-4-((((1s,3S)-3-(2-(5-chloro-6-
         (trifluoromethyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)cyclopentanol
A86      (2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)tetrahydrofuran-3,4-diol
A87      (2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((isopropyl((1r,3S)-3-(2-(5-
         (trifluoromethoxy)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A88      (2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(ethyl)amino)methyl)tetrahydrofuran-3,4-diol
A89      (2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(ethyl)amino)methyl)tetrahydrofuran-3,4-diol
A90      (2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A91      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((isopropyl((1r,3S)-3-(2-(5-(trifluoromethoxy)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A92      (2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)tetrahydrofuran-3,4-diol
A93      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((isopropyl((1s,3R)-3-(2-(5-(trifluoromethoxy)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A94      (2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((methyl((1r,3S)-3-(2-(5-
         (trifluoromethoxy)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A95      (2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((methyl((1s,3R)-3-(2-(5-
         (trifluoromethoxy)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A96      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((methyl((1r,3S)-3-(2-(5-(trifluoromethoxy)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A97      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((methyl((1s,3R)-3-(2-(5-(trifluoromethoxy)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A98      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A99      (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1s,3R)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
1A00     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((isopropyl(3-(2-(5-(trifluoromethoxy)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A101     (1R,2R,4S)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-4-((((1r,3R)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)cyclopentanol
A102     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(2,2,2-trifluoroethyl)amino)methyl)tetrahydrofuran-3,4-diol
A103     (1R,2R,4S)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-4-((((1s,3S)-3-(2-(5-chloro-6-
         (trifluoromethyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)cyclopentanol
A104     (1R,2R,4S)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-4-((((1s,3S)-3-(2-(5-(tert-butyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)cyclopentanol
A105     (1R,2R,4S)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-4-((((1r,3R)-3-(2-(5-chloro-6-
         (trifluoromethyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)cyclopentanol
A106     (1r,3S)-N-(((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)-3-(2-
         (5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)-N-isopropylcyclobutanamine oxide
A107     (R,1s,3R)-N-(((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)-3-
         (2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)-N-isopropylcyclobutanamine oxide
A108     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(1-hydroxy-2-methylpropan-2-yl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A109     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1s,3R)-3-(2-(5-(1-hydroxy-2-methylpropan-2-yl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A110     1-((3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-
         yl)methyl)(methyl)amino)cyclobutyl)methyl)-3-(4-(tert-butyl)phenyl)urea
A111     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(((3-(2-(5-cyclobutyl-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A112     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(((3-(2-(5-cyclopropyl-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A113     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((isopropyl(3-(2-(5-(2,2,2-trifluoroethyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A114     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1s,3R)-3-(2-(5-cyclobutyl-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A115     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-cyclobutyl-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A116     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-cyclopropyl-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A117     1-(2-(2-(3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-
         yl)methyl)(isopropyl)amino)cyclobutyl)ethyl)-1H-benzo[d]imidazol-5-yl)cyclobutanecarbonitrile
A118     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((isopropyl(3-(2-(5-(1-methoxy-2-methylpropan-2-yl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A119     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1s,3R)-3-(2-(5-cyclopropyl-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
A120     2-(2-(2-(3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-
         yl)methyl)(isopropyl)amino)cyclobutyl)ethyl)-1H-benzo[d]imidazol-5-yl)-2-methylpropanenitrile
A121     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((isopropyl((1s,3R)-3-(2-(5-(1-methoxy-2-methylpropan-2-
         yl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A122     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((isopropyl((1r,3S)-3-(2-(5-(1-methoxy-2-methylpropan-2-
         yl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A123     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((isopropyl((1s,3R)-3-(2-(5-(2,2,2-trifluoroethyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A124     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((isopropyl((1r,3S)-3-(2-(5-(2,2,2-trifluoroethyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A125     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(((3-(2-(5-cyclobutyl-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(methyl)amino)methyl)tetrahydrofuran-3,4-diol
A126     1-(2-(2-(3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-
         yl)methyl)(isopropyl)amino)cyclobutyl)ethyl)-1H-benzo[d]imidazol-5-yl)cyclopropanecarbonitrile
A127     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(((3-(2-(5-cyclopropyl-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(methyl)amino)methyl)tetrahydrofuran-3,4-diol
A128     2-(2-(2-((1S,3r)-3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-
         yl)methyl)(isopropyl)amino)cyclobutyl)ethyl)-1H-benzo[d]imidazol-5-yl)-2-methylpropanenitrile
A129     2-(2-(2-((1R,3s)-3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-
         yl)methyl)(isopropyl)amino)cyclobutyl)ethyl)-1H-benzo[d]imidazol-5-yl)-2-methylpropanenitrile
A130     1-(2-(2-(3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-
         yl)methyl)(methyl)amino)cyclobutyl)ethyl)-1H-benzo[d]imidazol-5-yl)cyclopropanecarbonitrile
A131     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-cyclobutyl-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(methyl)amino)methyl)tetrahydrofuran-3,4-diol
A132     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1s,3R)-3-(2-(5-cyclobutyl-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(methyl)amino)methyl)tetrahydrofuran-3,4-diol
A133     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-cyclopropyl-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(methyl)amino)methyl)tetrahydrofuran-3,4-diol
A134     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1s,3R)-3-(2-(5-cyclopropyl-1H-benzo[d]imidazol-2-
         yl)ethyl)cyclobutyl)(methyl)amino)methyl)tetrahydrofuran-3,4-diol
A135     1-(2-(2-((1S,3r)-3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-
         yl)methyl)(isopropyl)amino)cyclobutyl)ethyl)-1H-benzo[d]imidazol-5-yl)cyclopropanecarbonitrile
A136     1-(2-(2-((1R,3s)-3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-
         yl)methyl)(isopropyl)amino)cyclobutyl)ethyl)-1H-benzo[d]imidazol-5-yl)cyclopropanecarbonitrile
A137     1-(2-(2-((1S,3r)-3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-
         yl)methyl)(methyl)amino)cyclobutyl)ethyl)-1H-benzo[d]imidazol-5-yl)cyclopropanecarbonitrile
A138     1-(2-(2-((1R,3s)-3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-
         yl)methyl)(methyl)amino)cyclobutyl)ethyl)-1H-benzo[d]imidazol-5-yl)cyclopropanecarbonitrile
A139     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((isopropyl(3-(2-(5-(1-methylcyclopropyl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydrofuran-3,4-diol
A140     (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(((3-(2-(5-(1-methoxy-2-methylpropan-2-yl)-1H-
         benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)amino)methyl)tetrahydrofuran-3,4-diol

TABLE 2
Cmpd. No. Chemical Name
B1        (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((4-(5-tert-butyl-1H-benzo[d]imidazol-
          2-yl)butyl)(isopropyl)amino)methyl)cyclopentane-1,2-diol
B2        (1R,2S,3R,5S)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((4-(5-tert-butyl-1H-benzo[d]imidazol-
          2-yl)butyl)(isopropyl)amino)methyl)cyclopentane-1,2-diol
B3        1-(3-((((1S,2R,3S,4R)-4-(6-amino-9H-purin-9-yl)-2,3-
          dihydroxycyclopentyl)methyl)(methyl)amino)propyl)-3-(4-(tert-butyl)phenyl)urea
B4        (1S,2R,3R,5R)-3-(((4-(6-chloro-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-
          yl)butyl)(isopropyl)amino)methyl)-5-(4-(cyclopropylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-
          yl)cyclopentane-1,2-diol
B5        (1S,2R,3R,5R)-3-(((4-(6-chloro-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-
          yl)butyl)(methyl)amino)methyl)-5-(4-(cyclopropylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-
          yl)cyclopentane-1,2-diol
B6        (1R,2S,3R,5R)-3-(4-(cyclopropylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((isopropyl(4-(6-
          (trifluoromethyl)-1H-benzo[d]imidazol-2-yl)butyl)amino)methyl)cyclopentane-1,2-diol
B7        (1R,2S,3R,5R)-3-(4-(cyclopropylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((methyl(4-(6-
          (trifluoromethyl)-1H-benzo[d]imidazol-2-yl)butyl)amino)methyl)cyclopentane-1,2-diol
B8        (1R,2S,3R,5R)-3-(4-(cyclopropylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((4-(5,6-dichloro-1H-
          benzo[d]imidazol-2-yl)butyl)(methyl)amino)methyl)cyclopentane-1,2-diol
B9        (1R,2S,3R,5R)-3-(4-(cyclopropylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((4-(5,6-dichloro-1H-
          benzo[d]imidazol-2-yl)butyl)(isopropyl)amino)methyl)cyclopentane-1,2-diol trihydrochloride
B10       1-(3-((((1R,2R,3S,4R)-4-(6-amino-9H-purin-9-yl)-2,3-
          dihydroxycyclopentyl)methyl)(methyl)amino)propyl)-3-(4-(tert-butyl)phenyl)urea
B11       N-(4-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)butyl)-N-(((1R,2R,3S,4R)-4-(4-(cyclopropylamino)-7H-
          pyrrolo[2,3-d]pyrimidin-7-yl)-2,3-dihydroxycyclopentyl)methyl)methanesulfonamide
B12       N-(4-(6-chloro-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)butyl)-N-(((1R,2R,3S,4R)-4-(4-
          (cyclopropylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,3-
          dihydroxycyclopentyl)methyl)methanesulfonamide
B13       (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((4-(6-chloro-5-(trifluoromethyl)-1H-
          benzo[d]imidazol-2-yl)butyl)(methyl)amino)methyl)cyclopentane-1,2-diol
B14       (1R,2S,3R,5R)-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(((4-(6-chloro-5-(trifluoromethyl)-1H-
          benzo[d]imidazol-2-yl)butyl)(isopropyl)amino)methyl)cyclopentane-1,2-diol
B15       N-(((1R,2R,3S,4R)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,3-dihydroxycyclopentyl)methyl)-N-
          (4-(6-chloro-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)butyl)methanesulfonamide
B16       N-(((1R,2R,3S,4R)-4-(4-(cyclopropylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,3-
          dihydroxycyclopentyl)methyl)-N-(4-(5,6-dichloro-1H-benzo[d]imidazol-2-yl)butyl)methanesulfonamide
B17       N-(((1R,2R,3S,4R)-4-(4-(cyclopropylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,3-
          dihydroxycyclopentyl)methyl)-N-(4-(5-(trifluoromethyl)-1H-benzo[d]imidazol-2-
          yl)butyl)methanesulfonamide

TABLE 3
SAH
C1
C2
C64
C79
C80
C81
C83
C84
C85
C86
C89
C90
C91
C92
C93
C94
C95
C96
C97
C98
C112
C113
C114
C115
C116
C117
C118
C122
C123
C124
C125
C126
C127
C128
C129
C130
C131
C140
C141
C142
C143

TABLE 4
D1
D2
D3
D4
D5
D6
D7
D8
D9
D10
D11
D12
D13
D14
D15
D16
D17

As used herein, “alkyl”, “C₁, C₂, C₃, C₄, C₅ or C₆ alkyl” or “C₁-C₆ alkyl” is intended to include C₁, C₂, C₃, C₄, C₅ or C₆ straight chain (linear) saturated aliphatic hydrocarbon groups and C₃, C₄, C₅ or C₆ branched saturated aliphatic hydrocarbon groups.

As used herein, the term “cycloalkyl” refers to a saturated or unsaturated nonaromatic hydrocarbon mono- or multi-ring system having 3 to 30 carbon atoms (e.g., C₃-C₁₀). Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, and adamantyl. The term “heterocycloalkyl” refers to a saturated or unsaturated nonaromatic 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system having one or more heteroatoms (such as O, N, S, or Se). Examples of heterocycloalkyl groups include, but are not limited to, piperazinyl, pyrrolidinyl, dioxanyl, morpholinyl, and tetrahydrofuranyl.

The term “optionally substituted alkyl” refers to unsubstituted alkyl or alkyl having designated substituents replacing one or more hydrogen atoms on one or more carbons of the hydrocarbon backbone. Such substituents can include, for example, alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, amino (including alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety.

An “arylalkyl” or an “aralkyl” moiety is an alkyl substituted with an aryl (e.g., phenylmethyl (benzyl)). An “alkylaryl” moiety is an aryl substituted with an alkyl (e.g., methylphenyl).

As used herein, “alkyl linker” is intended to include C₁, C₂, C₃, C₄, C₅ or C₆ straight chain (linear) saturated divalent aliphatic hydrocarbon groups and C₃, C₄, C₅ or C₆ branched saturated aliphatic hydrocarbon groups. For example, C1-C6 alkyl linker is intended to include C₁, C₂, C₃, C₄, C₅ and C₆ alkyl linker groups.

“Alkenyl” includes unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double bond.

“Alkynyl” includes unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but which contain at least one triple bond.

Other optionally substituted moieties (such as optionally substituted alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl) include both the unsubstituted moieties and the moieties having one or more of the designated substituents.

“Aryl” includes groups with aromaticity, including “conjugated,” or multicyclic systems with at least one aromatic ring and do not contain any heteroatom in the ring structure. Examples include phenyl, benzyl, 1,2,3,4-tetrahydronaphthalenyl, etc.

“Heteroaryl” groups are aryl groups, as defined above, except having from one to four heteroatoms in the ring structure, and may also be referred to as “aryl heterocycles” or “heteroaromatics.” As used herein, the term “heteroaryl” is intended to include a stable 5- or 6-membered monocyclic or 7-, 8-, 9-, 10-, 11- or 12-membered bicyclic aromatic heterocyclic ring which consists of carbon atoms and one or more heteroatoms, e.g., 1 or 1-2 or 1-3 or 1-4 or 1-5 or 1-6 heteroatoms, or e.g. 1, 2, 3, 4, 5, or 6 heteroatoms, independently selected from the group consisting of nitrogen, oxygen and sulfur. The nitrogen atom may be substituted or unsubstituted (i.e., N or NR wherein R is H or other substituents, as defined). The nitrogen and sulfur heteroatoms may optionally be oxidized (i.e., N→O and S(O)_p, where p=1 or 2). It is to be noted that total number of S and O atoms in the aromatic heterocycle is not more than 1.

Examples of heteroaryl groups include pyrrole, furan, thiophene, thiazole, isothiazole, imidazole, triazole, tetrazole, pyrazole, oxazole, isoxazole, pyridine, pyrazine, pyridazine, pyrimidine, and the like.

Furthermore, the terms “aryl” and “heteroaryl” include multicyclic aryl and heteroaryl groups, e.g., tricyclic, bicyclic, e.g., naphthalene, benzoxazole, benzodioxazole, benzothiazole, benzoimidazole, benzothiophene, methylenedioxyphenyl, quinoline, isoquinoline, naphthrydine, indole, benzofuran, purine, benzofuran, deazapurine, indolizine.

In the case of multicyclic aromatic rings, only one of the rings needs to be aromatic (e.g., 2,3-dihydroindole), although all of the rings may be aromatic (e.g., quinoline). The second ring can also be fused or bridged.

As used herein, “carbocycle” or “carbocyclic ring” is intended to include any stable monocyclic, bicyclic or tricyclic ring having the specified number of carbons, any of which may be saturated, unsaturated, or aromatic. For example, a C₃-C₁₄ carbocycle is intended to include a monocyclic, bicyclic or tricyclic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 carbon atoms.

Examples of carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cycloheptenyl, cycloheptyl, cycloheptenyl, adamantyl, cyclooctyl, cyclooctenyl, cyclooctadienyl, fluorenyl, phenyl, naphthyl, indanyl, adamantyl and tetrahydronaphthyl. Bridged rings are also included in the definition of carbocycle, including, for example, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane and [2.2.2]bicyclooctane. A bridged ring occurs when one or more carbon atoms link two non-adjacent carbon atoms. In one embodiment, bridge rings are one or two carbon atoms. It is noted that a bridge always converts a monocyclic ring into a tricyclic ring. When a ring is bridged, the substituents recited for the ring may also be present on the bridge. Fused (e.g., naphthyl, tetrahydronaphthyl) and spiro rings are also included.

As used herein, “heterocycle” includes any ring structure (saturated or partially unsaturated) which contains at least one ring heteroatom (e.g., N, O or S). Examples of heterocycles include, but are not limited to, morpholine, pyrrolidine, tetrahydrothiophene, piperidine, piperazine and tetrahydrofuran.

Examples of heterocyclic groups include, but are not limited to, acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isatinoyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, methylenedioxyphenyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-oxadiazol5(4H)-one, oxazolidinyl, oxazolyl, oxindolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, piperidonyl, 4-piperidonyl, piperonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl and xanthenyl.

The term “substituted,” as used herein, means that any one or more hydrogen atoms on the designated atom is replaced with a selection from the indicated groups, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound. When a substituent is oxo or keto (i.e., ═O), then 2 hydrogen atoms on the atom are replaced. Keto substituents are not present on aromatic moieties. Ring double bonds, as used herein, are double bonds that are formed between two adjacent ring atoms (e.g., C═C, C═N or N═N). “Stable compound” and “stable structure” are meant to indicate a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.

When a bond to a substituent is shown to cross a bond connecting two atoms in a ring, then such substituent may be bonded to any atom in the ring. When a substituent is listed without indicating the atom via which such substituent is bonded to the rest of the compound of a given formula, then such substituent may be bonded via any atom in such formula. Combinations of substituents and/or variables are permissible, but only if such combinations result in stable compounds.

When any variable (e.g., R₁) occurs more than one time in any constituent or formula for a compound, its definition at each occurrence is independent of its definition at every other occurrence. Thus, for example, if a group is shown to be substituted with 0-2 R₁ moieties, then the group may optionally be substituted with up to two R₁ moieties and R₁ at each occurrence is selected independently from the definition of R₁. Also, combinations of substituents and/or variables are permissible, but only if such combinations result in stable compounds.

Compounds of the present invention that contain nitrogens can be converted to N-oxides by treatment with an oxidizing agent (e.g., 3-chloroperoxybenzoic acid (mCPBA) and/or hydrogen peroxides) to afford other compounds of the present invention. Thus, all shown and claimed nitrogen-containing compounds are considered, when allowed by valency and structure, to include both the compound as shown and its N-oxide derivative (which can be designated as N→O or N⁺—O⁻). Furthermore, in other instances, the nitrogens in the compounds of the present invention can be converted to N-hydroxy or N-alkoxy compounds. For example, N-hydroxy compounds can be prepared by oxidation of the parent amine by an oxidizing agent such as m-CPBA. All shown and claimed nitrogen-containing compounds are also considered, when allowed by valency and structure, to cover both the compound as shown and its N-hydroxy (i.e., N—OH) and N-alkoxy (i.e., N—OR, wherein R is substituted or unsubstituted C₁-C₆ alkyl, C₁-C₆ alkenyl, C₁-C₆ alkynyl, 3-14-membered carbocycle or 3-14-membered heterocycle) derivatives.

In the present specification, the structural formula of the compound represents a certain isomer for convenience in some cases, but the present invention includes all isomers, such as geometrical isomers, optical isomers based on an asymmetrical carbon, stereoisomers, tautomers, and the like. In addition, a crystal polymorphism may be present for the compounds represented by the formula. It is noted that any crystal form, crystal form mixture, or anhydride or hydrate thereof is included in the scope of the present invention. Furthermore, so-called metabolite which is produced by degradation of the present compound in vivo is included in the scope of the present invention.

“Isomerism” means compounds that have identical molecular formulae but differ in the sequence of bonding of their atoms or in the arrangement of their atoms in space. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers.” Stereoisomers that are not mirror images of one another are termed “diastereoisomers,” and stereoisomers that are non-superimposable mirror images of each other are termed “enantiomers” or sometimes optical isomers. A mixture containing equal amounts of individual enantiomeric forms of opposite chirality is termed a “racemic mixture.”

It is to be understood that the compounds of the present invention may be depicted as different chiral isomers or geometric isomers. It should also be understood that when compounds have chiral isomeric or geometric isomeric forms, all isomeric forms are intended to be included in the scope of the present invention, and the naming of the compounds does not exclude any isomeric forms.

For example, compounds of Formula (II) include those of the following chiral isomers and geometric isomers.

Furthermore, the structures and other compounds discussed in this invention include all atropic isomers thereof. “Atropic isomers” are a type of stereoisomer in which the atoms of two isomers are arranged differently in space. Atropic isomers owe their existence to a restricted rotation caused by hindrance of rotation of large groups about a central bond. Such atropic isomers typically exist as a mixture, however as a result of recent advances in chromatography techniques, it has been possible to separate mixtures of two atropic isomers in select cases.

“Tautomer” is one of two or more structural isomers that exist in equilibrium and is readily converted from one isomeric form to another. This conversion results in the formal migration of a hydrogen atom accompanied by a switch of adjacent conjugated double bonds. Tautomers exist as a mixture of a tautomeric set in solution. In solutions where tautomerization is possible, a chemical equilibrium of the tautomers will be reached. The exact ratio of the tautomers depends on several factors, including temperature, solvent and pH. The concept of tautomers that are interconvertable by tautomerizations is called tautomerism.

Of the various types of tautomerism that are possible, two are commonly observed. In keto-enol tautomerism a simultaneous shift of electrons and a hydrogen atom occurs. Ring-chain tautomerism arises as a result of the aldehyde group (—CHO) in a sugar chain molecule reacting with one of the hydroxy groups (—OH) in the same molecule to give it a cyclic (ring-shaped) form as exhibited by glucose.

Common tautomeric pairs are: ketone-enol, amide-nitrile, lactam-lactim, amide-imidic acid tautomerism in heterocyclic rings (e.g., in nucleobases such as guanine, thymine and cytosine), amine-enamine and enamine-enamine. Benzimidazoles also exhibit tautomerism, when the benzimidazole contains one or more substituents in the 4, 5, 6 or 7 positions, the possibility of different isomers arises. For example, 2,5-dimethyl-1H-benzo[d]imidazole can exist in equilibrium with its isomer 2,6-dimethyl-1H-benzo[d]imidazole via tautomerization.

Another example of tautomerism is shown below.

It is to be understood that the compounds of the present invention may be depicted as different tautomers. It should also be understood that when compounds have tautomeric forms, all tautomeric forms are intended to be included in the scope of the present invention, and the naming of the compounds does not exclude any tautomer form.

The term “crystal polymorphs”, “polymorphs” or “crystal forms” means crystal structures in which a compound (or a salt or solvate thereof) can crystallize in different crystal packing arrangements, all of which have the same elemental composition. Different crystal forms usually have different X-ray diffraction patterns, infrared spectral, melting points, density hardness, crystal shape, optical and electrical properties, stability and solubility. Recrystallization solvent, rate of crystallization, storage temperature, and other factors may cause one crystal form to dominate. Crystal polymorphs of the compounds can be prepared by crystallization under different conditions.

Compounds of the invention may be crystalline, semi-crystalline, non-crystalline, amorphous, mesomorphous, etc.

The compounds of any of the Formulae disclosed herein or the DOT1L inhibitors identified by the methods of the invention include the compounds themselves, as well as their N-oxides, salts, their solvates, and their prodrugs, if applicable. A salt, for example, can be formed between an anion and a positively charged group (e.g., amino) on the compound or inhibitor (e.g., a substituted nucleoside compound such as a substituted purine or 7-deazapurine compound). Suitable anions include chloride, bromide, iodide, sulfate, bisulfate, sulfamate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate, glutamate, glucuronate, glutarate, malate, maleate, succinate, fumarate, tartrate, tosylate, salicylate, lactate, naphthalenesulfonate, and acetate. Likewise, a salt can also be formed between a cation and a negatively charged group (e.g., carboxylate) on the compound or inhibitor (e.g., a substituted nucleoside compound such as a substituted purine or 7-deazapurine compound). Suitable cations include sodium ion, potassium ion, magnesium ion, calcium ion, and an ammonium cation such as tetramethylammonium ion. The compound or inhibitor (e.g., a substituted nucleoside compound such as a substituted purine or 7-deazapurine compound) also include those salts containing quaternary nitrogen atoms. Examples of prodrugs include esters and other pharmaceutically acceptable derivatives, which, upon administration to a subject, are capable of providing active substituted nucleoside compound such as a substituted purine or 7-deazapurine.

Additionally, the compounds of the present invention, for example, the salts of the compounds, can exist in either hydrated or unhydrated (the anhydrous) form or as solvates with other solvent molecules. Nonlimiting examples of hydrates include hemihydrates, monohydrates, dihydrates, trihydrates, etc. Nonlimiting examples of solvates include ethanol solvates, acetone solvates, etc.

“Solvate” means solvent addition forms that contain either stoichiometric or non stoichiometric amounts of solvent. Some compounds have a tendency to trap a fixed molar ratio of solvent molecules in the crystalline solid state, thus forming a solvate. If the solvent is water the solvate formed is a hydrate; and if the solvent is alcohol, the solvate formed is an alcoholate. Hydrates are formed by the combination of one or more molecules of water with one molecule of the substance in which the water retains its molecular state as H₂O. A hemihydrate is formed by the combination of one molecule of water with more than one molecule of the substance in which the water retains its molecular state as H₂O.

As used herein, the term “analog” refers to a chemical compound that is structurally similar to another but differs slightly in composition (as in the replacement of one atom by an atom of a different element or in the presence of a particular functional group, or the replacement of one functional group by another functional group). Thus, an analog is a compound that is similar or comparable in function and appearance, but not in structure or origin to the reference compound.

As defined herein, the term “derivative” refers to compounds that have a common core structure, and are substituted with various groups as described herein. For example, all of the compounds represented by Formula (I) are substituted purine compounds or substituted 7-deazapurine compounds, and have Formula (I) as a common core.

The term “bioisostere” refers to a compound resulting from the exchange of an atom or of a group of atoms with another, broadly similar, atom or group of atoms. The objective of a bioisosteric replacement is to create a new compound with similar biological properties to the parent compound. The bioisosteric replacement may be physicochemically or topologically based. Examples of carboxylic acid bioisosteres include, but are not limited to, acyl sulfonimides, tetrazoles, sulfonates and phosphonates. See, e.g., Patani and LaVoie, Chem. Rev. 96, 3147-3176, 1996.

The present invention is intended to include all isotopes of atoms occurring in the present compounds. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include tritium and deuterium, and isotopes of carbon include C-13 and C-14.

The present invention provides methods for the synthesis of the compounds of any of the Formulae disclosed herein. The present invention also provides detailed methods for the synthesis of various disclosed compounds of the present invention according to the schemes and the Examples described in WO2012/075381, WO2012/075492, WO2012/082436, and WO2012/75500, the contents of which are hereby incorporated by reference in their entireties.

Throughout the description, where compositions are described as having, including, or comprising specific components, it is contemplated that compositions also consist essentially of, or consist of, the recited components. Similarly, where methods or processes are described as having, including, or comprising specific process steps, the processes also consist essentially of, or consist of, the recited processing steps. Further, it should be understood that the order of steps or order for performing certain actions is immaterial so long as the invention remains operable. Moreover, two or more steps or actions can be conducted simultaneously.

All percentages and ratios used herein, unless otherwise indicated, are by weight. Other features and advantages of the present invention are apparent from the different examples. The provided examples illustrate different components and methodology useful in practicing the present invention. The examples do not limit the claimed invention. Based on the present disclosure the skilled artisan can identify and employ other components and methodology useful for practicing the present invention.

In the synthetic schemes described herein, compounds may be drawn with one particular configuration for simplicity. Such particular configurations are not to be construed as limiting the invention to one or another isomer, tautomer, regioisomer or stereoisomer, nor does it exclude mixtures of isomers, tautomers, regioisomers or stereoisomers.

Compounds described herein are assayed for modulation of activity, for example, histone methylation, modulation of cell growth and/or IC₅₀, described in the examples below. IC₅₀ values are presented as A=<0.1 μM; B=>0.1 μM and <1 μM; C=>1 μM and <10 μM; and D=>10 μM and <50 μM.

Compound DOT1L IC50 (μM)
A2       0.00074
A3       0.00073
A5       0.00059
A69      0.00251
A75      0.00059
A86      0.00062
A87      0.0008
A91      0.00218
A93      0.00292

All publications and patent documents cited herein are incorporated herein by reference as if each such publication or document was specifically and individually indicated to be incorporated herein by reference. Citation of publications and patent documents is not intended as an admission that any is pertinent prior art, nor does it constitute any admission as to the contents or date of the same. The invention having now been described by way of written description, those of skill in the art will recognize that the invention can be practiced in a variety of embodiments and that the foregoing description and examples below are for purposes of illustration and not limitation of the claims that follow.

EXAMPLES

Assays of Enzymatic Activity

Unless otherwise indicated, assays of DOT1L enzymatic activity were performed under balanced conditions (all substrates present at concentrations equal to their respective K_M values) using a radiometric assay of S-[methyl-³H]adenosyl-L-methionine transfer from SAM to chicken erythrocyte nucleosomes as previously described. Reactions were initiated by addition of S-[methyl-³H]adenosyl-L-methionine and allowed to run at room temperature for 120 minutes before being quenched by the addition of 800 μM cold SAM.

Compound IC₅₀ values were determined from assays of enzymatic activity in which compound was titrated into reaction mixtures by 3-fold serial dilution from DMSO stocks. For each titration, 10 concentrations of inhibitor were used along with 100% inhibition (2.5 μM SAH) and 0% inhibition (1 μL of neat DMSO per well) controls. Plots of residual enzyme velocity as a function of inhibitor concentration were fit to a standard Langmuir isotherm equation (12) to derive estimates of the IC₅₀ value of the compound. As described herein, the inhibition modality of key compounds within the aminonucleoside series were tested and always found to be competitive with SAM and noncompetitive with respect to nucleosome substrate. For most compounds, the K_i value was calculated from the IC₅₀ value using the appropriate equation for competitive inhibition with respect to SAM.

For selected compounds, the inhibition modality with respect to the two substrates (SAM and nucleosomes) were determined by dual titration of compound and varied substrate concentration while holding the other substrate fixed at its K_M value. Plots of velocity as a function of varied substrate at multiple inhibitor concentrations were globally fit to a general equation for enzyme inhibition using Graphpad Prism. Selection of the modality for each data set was done by evaluating the value of α, a term related to the degree of cooperative or anticooperative interaction between substrate and inhibitor binding, as previously described. A value of α≧10 was taken as consistent with competitive inhibition, while a value of α≦0.1 was taken as consistent with uncompetitive inhibition. Values of α between 10 and 0.1 were considered to be consistent with noncompetitive inhibition.

Compounds that displayed an IC₅₀ value within 50-fold of the enzyme concentration used in initial assays ([E]=0.25 nM) were treated as tight binding inhibitors. In this case, the K_i value was determined by measuring the IC₅₀ value of the compound (vide supra) at varying concentrations of enzyme from 5 nM to 0.25 nM. A plot of IC₅₀ as a function of enzyme concentration was fit to a linear equation and the y-intercept value was equivalent to K_i(1+[S]/K_M) where [S] and K_M refer to SAM, the substrate with which these inhibitors compete. Knowing the values of [S] and K_M used in the assay, the K_i value was then calculated from the y-intercept value.

Determination of Ligand Association and Dissociation Rate Constants

Ligand association and dissociation rate constants were determined by surface plasmon resonance (SPR). DOT1L was stored in 20 mM Tris-HCl, 200 mM NaCl, 1 mM EDTA, 1 mM DTT, pH 7.8 and immobilized by direct amine coupling, diluting enzyme into coupling buffer containing 10 mM Hepes pH 7.4, 1 mM TCEP. Immobilization run buffer contained 10 mM Hepes pH 7.4, 150 mM NaCl, 500 μM TCEP, and approximately 10,000 RUs (response units) of DOT1L was captured. A reference channel of a surface that was activated in parallel and blocked was created in a second flow cell was also created. Data was captured on either a Biacore 4000 (chip CM5) or a Biorad ProteOn (chip GLM).

K_d determinations were determined using run buffer containing 20 mM Tris pH 8.0, 10 mM NaCl, 100 mM KCl, 0.002% Tween-20, 500 μM TCEP, 2% DMSO, with the following injection parameters: 30 μl/min flow rate, with a 30 second association phase followed by monitoring dissociation for 30 seconds. Experiments were carried out at 25° C.

Cell Proliferation Assay

The human leukemia cell line MV4-11 harboring the MLL-AF4 translocation was obtained from ATCC (CRL-9591). Cells were grown in Iscove's Modified Dulbecco's Medium (IMDM) with 10% Fetal Bovine Serum (FBS). All cell culture reagents were purchased from Invitrogen Life Technologies and cells were maintained in a humidified incubator set to 37° C., 5% CO₂.

Cell proliferation was assessed by plating, in triplicate, exponentially growing MV4-11 cells in a 96 well plate at a density of 3×10⁴ cells/well in a final volume of 150 μL. Cells were incubated in the presence of compound at increasing concentrations up to 50 μM. Viable cell numbers were determined every 3-4 days for a total of 14 days using the Guava Viacount assay (Millipore #4000-0040). Analysis was performed on a Guava EasyCyte Plus instrument (Millipore) according to the manufacturer's protocol. On days of cell counts, growth media and compound were replaced and cells split back to a density of 5×10⁴ cells/well. Total cell number is expressed as split-adjusted viable cells per well. IC₅₀ values were determined from concentration dependent curves at day 14 using the Graphpad Prism software.

H3K79me2 Quantitative ELISA

Exponentially growing MV4-11 cells were seeded in a 12-well plate at 2×10⁵ cells/well in a final volume of 2 mls. Cells were incubated in the presence of increasing concentrations of Compound C94, C118, or D16 up to 50 μM. Control cells were treated with 0.2% DMSO control. Cells (1-2×10⁶) were harvested after 96 hours of compound incubation and histones were extracted. An indirect enzyme-linked immunosorbent assay (ELISA) using acid extracted histones was run using matching microtiter plates (Immulon 4HBX #3855, Thermo Labsystems). Plates were coated for total H3 and H3K79me2 detection with either 75 ng or 1500 ng/well of histones respectively. The coating antigen was diluted in coating buffer (PBS+0.05% BSA) for a final volume of 100 μl and allowed to incubate overnight. The plates were blocked with 300 μl blocking buffer (PBST+2% BSA) for 2 hours at RT, followed by a 2 hour incubation with 100 μl primary antibody (1:750 H3K79me2, CST 5472; or 1:5000 total H3, Abcam ab1791) diluted in blocking buffer at RT. 100 μl of HRP tagged goat-anti-rabbit antibody (1:4000, CST 7074) in blocking buffer was added and allowed to incubate for 2 hours at RT. The reaction was visualized with 100 μl 3,3′,5,5′ tetramethylbenzidine substrate (TMBS, BioFx Laboratories) and stopped with an equivalent volume of 1 N sulfuric acid. Plates were read at 450 nm on an M5e plate spectrophotometer. Following each step, plates were washed 3 times with wash buffer (PBST), with an additional wash included following secondary antibody.

Quantitative Real-Time PCR Analysis

Exponentially growing MV4-11 cells were plated in a 12 well plate at 2×10⁵ cells/well in a final volume of 2 mL. Cells were incubated with increasing concentration of test compounds (e.g., Compounds C94, C118, and D16 up to 50 μM for 6 days. Compound and media were refreshed on day 4 and cells split back to 5×10⁵ cells/well. Cells were pelleted and processed as previously described.

Example 1

Structure Determination of DOT1L with Compound

The production of His-DOT1L-1-416 (SEQ ID NO: 1) and crystallization with SAM have been reported previously. Compound C1 was pre-incubated with DOT1L-1-416 (SEQ ID NO: 1) in 10 fold molar excess and then co-crystallization was set up with the hanging drop method using solution containing 100 mM sodium acetate, 1.8-2.0 M ammonium sulfate, 5 mM Tris(2-carboxyethyl)phosphine (TCEP), pH 5.5, at 20 OC. In order to observe the protein at a physiological pH, crystals were transferred using nylon loops into a pH 7.5 Tris buffer (100 mM Tris-HCl (pH 7.5), 2.0 M ammonium sulfate, 5 mM TCEP). This transfer was done stepwise by soaking the crystals over the course of one hour in successive mixtures of acetate and Tris buffers. The crystals were equilibrated in the final Tris buffer at pH 7.5 overnight at 20° C. The crystal were next transferred stepwise into cryoprotectant (25 mM Tris-HCl, 2.0 M ammonium sulfate, 30% glycerol, pH 7.5), and flash-frozen in liquid nitrogen. Data collection was done at beamline X12B at the National Synchrotron Light Source at Brookhaven National Labs, Upton, N.Y.

For Compounds C118 and D16, DOT1L bound structures were obtained by the soaking method. The DOT1L-SAM crystals were cross-linked by exposing the crystal containing hanging drop over the vapor of 1 μl of 25% glutaraldehyde, pH 3.0, for 1 hr (13, 14) and then soaked with mother liquor containing 1 mM compound overnight. The crystals were cryo-protected with 35% glucose in mother liquor and flash-frozen in liquid nitrogen. The diffraction data sets were collected at beamline 17U at the Shanghai Synchrotron Radiation Facility. All data were processed by HKL2000. Structures were solved by molecular replacement (Phaser) using the DOT1L-SAM structure (PDB code:3QOW) with the SAM molecule removed as a search model. Refinement was carried out by Refmac5 and the model building was carried out by COOT. Detailed information of the diffraction data, refinement, and structure statistics are provided in Table 7 below. The 2fo-fc maps for the three ligands are shown in FIG. 10A-C. The coordinates for the crystal structures have been deposited with PDB code of 4EK9 (DOT1L-Compound C1), 4EKG (DOT1L-Compound C118) and 4EKI (DOT1L-Compound D16). Structural coordinates for DOTDOT L-Compound D16 and DOT1L-Compound A2 are respectively provided in Tables S1 and S2 in the Appendix.

Example 2

Designing DOT1L Inhibitors

Mechanism-Guided Design Tenets

In the case of DOT1L, methyl transfer from the thiomethyl moiety of SAM to the ε-N of the bound side chain of lysine 79 of histone H3 (H3K79) proceeds through a simple S_N2 mechanism, requiring stringent alignment of the molecular orbitals of the methyl donor and acceptor atoms. The crystal structures of DOT1L bound to SAM and to the reaction product SAH illustrate a highly ordered active site with superimposable SAM and SAH configurations in the bound structure. The thiomethyl group of SAM is directed into a contiguous channel that forms the lysine binding pocket of the enzyme, thus facilitating facile group transfer once the ternary enzyme-SAM-histone complex has formed. Steady state kinetic analysis suggests that DOT1L functions by a distributive mechanism, requiring dissociation of the enzyme from the histone substrate after each round of lysine 79 methylation. The product SAH binds to DOT1L with relatively high affinity (K_i=320 nM), suggesting that product dissociation may be at least partially rate-limiting to enzyme turnover.

In one aspect of the invention, the above biochemical data provided a starting point for inhibitor design. The drug design started based on the structure of the reaction product SAH, with the following key objectives. First objective was to reduce the polar surface area of the ligand by replacement of charged and/or polar functionalities. Second objective was to engage recognition elements within both the SAM/SAH binding pocket and the adjacent lysine binding pocket to gain the affinity advantages of bisubstrate inhibitors. Lastly, these two goals should be accomplished while reasonable ligand efficiency is maintained and/or the pharmacological tractability of the compound series is improved.

The initial approach towards the above stated objectives was to replace the highly polarizable sulfur atom, eliminate the charged groups on the amino acid portion of SAH, and minimize the molecular mass contributed to by the amino acid side chain. To this end, the homocysteine moiety of SAH was replaced with a simple dimethyl amine to create a minimal pharmacophore, as represented by Compound C1. Despite these significant changes, Compound C1 retained a reasonable degree of binding affinity for DOT1L (K_i=38 μM); the binding free energy change (ΔΔG_binding) for this compound, relative to SAH, was only 2.9 kcal/mol (at 25° C.). Additionally, crystallographic analysis of the binary complex of DOT1L and Compound C1 confirmed that, despite the S to N substitution, the compound binds within the active site of the enzyme in the same configuration as SAM. These data establish the utility of Compound C1 as a founder molecule for SAR (structure-activity relationship) elaboration.

Structure-Activity Relationships for SAH Mimetic DOT1L Inhibitors

The modification of Compound C1 by independent alterations to the alkyl side chains appended to the nitrogen atom of the 5′ amine. Fixing one substituent as methyl, the second substituent was systematically varied with low molecular weight substituents with more effectively engaging recognition elements near the juxtaposition of the SAM and lysine binding pockets. To this end, a library of 25 compounds were prepared and tested for DOT1L inhibition. From this library the Compound C2 was identified, which demonstrated a DOT1L K_i of 12 μM.

The isopropyl group of Compound C2 was speculated to reach into the lysine binding pocket. Based on this assumption, this functionality was further developed to further engage elements within this channel and simultaneously engage recognition elements within the amino acid binding pocket by varying the substituent. In the course of library building for these purposes, key intermediate species along the synthetic route were tested. The FMoc-protected intermediate Compound C64 displayed potency for inhibition of DOT1L, with a K_i of 20 μM. The instability of this compound precluded detailed structural characterization by crystallography. This finding did, however, lead to replacing the functionality with a short tether, linked to a large hydrophobic group. Replacing the FMoc group with a tert-butyl phenyl urea resulted in Compound C94, which showed a marked improvement in potency (K_i=845 nM). Combining this replacement with an extension of the tether group by one methylene (from ethyl to propyl) led to even greater target engagement, as exemplified by Compound C118, a compound with a K_i of 13 nM.

In one aspect of the invention, tolerance of DOT1L inhibitors for substitutions within the nucleoside portion of the pharmacophore was determined. In general, substitutions on the nucleoside were not well tolerated. However, the ring nitrogen at position 7 could be substituted by carbon; the resulting deazapurine compounds demonstrated potent inhibition of DOT1L as exemplified by compound D8, an inhibitor displaying a K_i of 4 nM.

Combining the 7 deazapurine moiety with the tert-butyl phenyl urea and 5′-amino isopropyl groups (vide supra) yielded compound D16. As previously described, D16 is a potent (K_i=300 μM), selective inhibitor of DOT1L that demonstrates activity in inhibiting intracellular methylation of H3K79 and selective killing of MLL-rearranged leukemia cell lines. This compound also demonstrated a statistically significant survival advantage in an aggressive, disseminated mouse model of MLL-rearranged leukemia.

Conformational Adaptation Drives Inhibitor Potency and Long Residence Time

Conformational adaptation appears to play a critical role in driving inhibitor potency among the aminonucleoside inhibitors of DOT1L.

Table 5 below summarizes the kinetics of inhibitor association and dissociation with DOT1L for the enzymatic product SAH and for three key compounds (Compounds C94, C118 and D16), as measured by surface plasmon resonance.

TABLE 5
	Ki	Kd	kon	koff
Compound	(nM)	(nM) a	(M−1s−1)	(s−1)	τ (s.)
SAH	320 ± 104 b	71 ± 40	1.4 ± 0.5 (×106)	0.1 ± 0.04	10 ± 1
C94	845 ± 472 b	167 ± 100	1.2 ± 0.8 (×106)	0.2 ± 0.09	5 ± 3
C118	13 ± 7 b	1.7 ± 0.2	1.20 ± 0.1 (×107)	0.02 ± 0.001	50 ± 3
D16	0.30 ± 0.02 c	0.10 ± 0.02	3.0 ± 0.4 (×106)	3 ± 0.3 (×10−4)	3333 ± 300
a Kd calculated as koff/kon.
b Errors represented as standard deviation (SD)
c Ki determined from concentration-dependent effects of compound on enzyme activity as described in Materials and Methods; error represented as standard error of measurement (SEM)

First, as noted above, there was a significant jump in target potency between C94 and C118 (ΔΔG_binding=2.3-2.5 kcal/mol at 25° C.) and again between C118 and D16 (ΔΔG_binding=2.4-2.9 kcal/mol at 25° C.). The enhancement in target potency seen across this series appears to be driven by a reduction in the dissociation rate of the inhibitors from the binary enzyme-inhibitor complex (k_off) which results in a dramatic change in the residence time (τ) of the binary complex from 5 seconds to 1 hour in going from C94 to D16; while the dissociation rate constants and residence times change by over three orders of magnitude among these compounds, the association rate constant (k_on) is virtually invariant across the pharmacophore series and is several orders of magnitude slower than the calculated diffusion limit. More advanced inhibitors within the aminonucleoside series continue this trend, displaying residence times greater than 24 hours with no attendant change in association rate constant (such as Compound A2).

The relatively slow association rate constants seen for SAH and the aminonucleosides also suggest a conformational gating of compound access to the SAM/SAH binding site. The upper limit of the association rate constant for diffusion-limited small molecule binding to a protein has been estimated to be on the order of 10⁹ M⁻¹s⁻¹. More typically values of the association rate constant for small molecule substrates binding to enzymes are about 10⁷ M⁻¹s⁻¹ and typical values for the residence time of enzyme substrates and products are in the millisecond to second range (23). Thus, even for the natural product of the enzyme, SAH, the rates of association and dissociation are slow relative to other natural ligands of enzymes. The crystal structures of SAM and SAH bound to DOT1L revealed an occluded active site with no clear, unobstructed pathway from bulk solvent to the active site for compound association or dissociation; thus some conformational adaptation must attend enzyme turnover in order for substrate to access the binding pocket and for product to be released.

These data also imply conformational adaptation of the enzyme in response to more potent (e.g., Compounds C118 and D16) inhibitor binding. Two possible conformational mechanisms are consistent with the data presented in Table 5. The first is referred to as a conformational selection mechanism in which the free enzyme exists in two conformational states that are in (slow) equilibrium with one another: a state that binds inhibitor and one that does not. Binding of the inhibitor shifts the equilibrium in favor of the inhibitor-binding conformation. The second mechanism is referred to as the induced-fit mechanism. In this model the inhibitor binds to the enzyme in a non-optimal conformational state and then induces a conformational adjustment of the enzyme to create a more complementary, tighter binding state of the binary enzyme-inhibitor complex. A third mechanism of slow association and slow dissociation results from situations in which the conformation of the enzyme does not change, but other factors limit the rate of ligand binding and dissociation. In this third situation, binding is often gated by the need for slow displacement of structured water molecules within the active site, displacement of metal binding ligands, and similar slow processes that are distinct from conformational adjustments of the protein per se.

The induced-fit mechanism is predominant among enzyme-inhibitor interactions. However the current data do not allow one to definitively distinguish between the two conformational adaptation models described above. In either case, the low-affinity conformational state appears to be kinetically (and thermodynamically) insignificant in terms of inhibitor interactions. This is evident from the excellent agreement between the K_i values for the inhibitor series, determined from the concentration dependent effects of compounds on enzyme activity, and the K_d values determined from the SPR binding experiments (Table 5). The K_d values in Table 5 are calculated simply as the ratio of k_off over k_on, thus assuming a single step binding and dissociation mechanism. If an intervening conformational state were kinetically significant in the inhibitor binding pathway, one would expect to see biphasic association curves in the enzymatic assay or the SPR binding or both. The good agreement between the K_i and simply calculated K_d values here argues against a significant kinetic role for an intervening conformational state. A similar situation is encountered in other enzyme-inhibitor systems that work through an induced-fit mechanism for which the initial encounter complex is kinetically insignificant and rapidly isomerizes to the final conformational state of the tight-binding enzyme-inhibitor complex.

Structural Changes Attending Inhibitor Binding

The inference drawn from the binding kinetics of conformational adaptation in DOT1L-inhibitor interactions is supported by crystallographic analysis of the structures of DOT1L-inhibitor binary complexes. Steady state kinetic analysis of DOT1L inhibition by the aminonucleosides consistently demonstrated competitive inhibition with respect to SAM and noncompetitive inhibition with respect to nucleosome (as exemplified for Compound D16 in FIG. 2). This kinetic characterization is consistent with the crystallographic data that demonstrates compound binding within the SAM/SAH binding pocket for all tested compounds. As described above, the structures of the founder Compound C1 and SAH are virtually superimposable (FIG. 3). The more potent Compounds C118 and D16 both contain an extended (i.e., propyl) tether and terminal hydrophobic groups appended to the 5′ amino nitrogen. It was initially expected that these extended structures would reach into the proximal lysine binding channel of the enzyme, creating a bisubstrate-like mode of inhibitor interaction. However, the crystal structure of DOT1L-Compound C118 reveals an unanticipated mode of interaction with the enzyme.

The DOT1L-Compound C118 structure reveals that the inhibitor reaches into a heretofore-unrecognized pocket immediately adjacent to the amino acid binding subsite of the SAM/SAH binding pocket of the enzyme (FIG. 4). This pocket—which does not exist in the structures of the enzyme with SAM, SAH or Compound C1—is opened up by the tert-butyl phenyl urea functionality of Compound C118. More specifically, the crystal structure of C118 reveals a number of novel interactions with DOT1L. For example, the charged 5′-amino group of the compound forms a hydrogen bond with the carbonyl oxygen of Gly163. The urea region occupies the binding site of the amino acid region of SAM. The terminal propyl nitrogen of the urea interacts with the side chain oxygen atom of Asp161 in the same binding mode as the carboxylate nitrogen atom in SAM. The urea carbonyl oxygen interacts with the nitrogen atom of Asn241, similar to the interaction of one of the carboxylate oxygen atoms of SAM. In addition, the proximal nitrogen atom of the urea (attached to the aromatic ring) coordinates with Asp161 (FIG. 4A). The steric bulk of the tert-butyl phenyl opens up the novel hydrophobic pocket by changing the side chain conformation of Phe239, Tyr312, Met147 and Leu143, inducing a significant conformational change in the 130s' loop to flip Thr139 (a residue that otherwise interacts with the carboxylate terminus of SAM) away from the SAM binding pocket (FIG. 4B). The movement of Tyr312 causes a change in a loop consisting of residues 302-312 (300s' loop). These changes result in both the 130s' and 300s' loops of DOT1L becoming disordered (FIG. 4C).

The crystal structure of the DOT1L-D16 complex reveals D16 binds to DOT1L in a similar manner as C118, with the 5′-amino isopropyl group occupying a region near that occupied by the methyl group of the thiomethyl on SAM (FIG. 5). Thus, the high potency, longer residence time compounds C118 and D16 are associated with a novel conformation of the enzyme that expands the contiguous active site cavity to include a new pocket; the crystal structures of these compounds suggest that these inhibitors “punch through” a protein wall to create this new pocket and to thus engage recognition elements both within the SAM/SAH binding pocket and the newly formed hydrophobic pocket. Because this conformational change is unique to DOT1L, these compounds show excellent selectivity against other PMTs (9).

In addition to the protein structural changes that attend potent inhibitor binding, it is often the case that inhibitor-induced displacement of key structural water molecules within enzyme active sites is a critical component of high-affinity ligand interactions. This may be a contributing factor in the tight-binding interactions between DOT1L and the aminonucleoside inhibitors presented here. However, the resolution of the various enzyme-inhibitor co-crystal structures is not sufficient for us to make any definitive statements with regard to the role of structural water molecule displacement in the binding of these compounds to DOT1L.

Correlation of Enzyme-Inhibitor Affinity with Cellular Activity

Inhibition of DOT1L is expected to lead to a concentration-dependent diminution of H3K79 methylation levels in treated cells. For cells bearing the chromosomal translocation of the MLL gene, the diminution of H3K79 methylation is expected to translated into reduced transcription of leukemogenic genes such as HOXA9(27) and thus to a concomitant inhibition of cell proliferation. It was demonstrated that the potent, selective DOT1L inhibitor D16 indeed leads to concentration-dependent inhibition of intracellular H3K79 dimethylation (H3K79me2), of HOXA9 gene transcription and antiproliferative effects selectively for MLL-rearranged leukemia cells. Hence, there appears to be a correlative relationship between DOT1L target engagement, reduction in intracellular formation of the enzyme product (H3K79me2) and downstream transcriptional events leading to antiproliferative efficacy for D16. In this study, these observations were extended to other members of the aminonucleoside series to establish more firmly the relationship between target engagement and phenotypic effects of DOT1L inhibitors.

Compounds C94, C118 and D16 provide a structurally related series of DOT1L inhibitors, spanning almost 4 orders of magnitude in target affinity, with which to test the relationship between enzyme inhibition and cellular efficacy. Various concentrations of each of these compounds were applied to MV4-11 cells bearing a chromosomal rearrangement of the MLL gene and the impact on H3K79me2 level, HOXA9 message and cell proliferation were assessed at appropriate time points, taking into account the distinct kinetics of compound impact on each of these cellular parameters. Table 6 below summarizes the results of these studies.

	TABLE 6
	Cellular IC50 μM
Com-		H3K79	HOXA9
pound	Ki (nM)	Methylation	mRNA	Proliferation
C94	845 ± 472	28 ± 25	>50	>50
C118	13 ± 7	0.272 ± 0.014	6.9 ± 0.5	4.9 ± 3.9
D16	0.30 ± 0.02	0.005 ± 0.003	0.83 ± 0.17	0.146 ± 0.072
Errors represented as standard deviation (SD)

Consistent with our mechanistic hypothesis, the data in Table 6 illustrate a clear relationship between enzyme engagement, inhibition of intracellular histone methylation, selective effects on gene transcription and antiproliferative efficacy. As was previously reported for D16, each of these DOT1L inhibitors showed selective inhibition of intracellular H3K79 methylation without effect on other histone methyl marks. Further, the antiproliferative effects of each of these DOT1L inhibitors were specific to MLL-rearranged leukemia cell lines; other leukemia cell lines without the chromosomal rearrangement of the MLL gene were essentially unaffected (antiproliferative IC₅₀>50 μM) by this series of DOT1L inhibitors. These data provide compelling evidence for a causal relationship between DOT1L inhibition and selective cell killing of MLL-rearranged leukemia cells by the aminonucleoside compound series.

The potent and selective inhibition of DOT1L by the aminonucleoside series translates into potent and selective inhibition of intracellular H3K79 methylation and to selective cell killing for leukemic cells bearing the MLL chromosomal translocation. The quantitative correlation between target engagement, intracellular inhibition of H3K79 methylation, and antiproliferative effects is striking, and leaves little doubt that the selective phenotypic effects of these compounds are driven directly by ablation of DOT1L enzymatic activity. These data provide a solid foundation upon which further optimization of DOT1L inhibitors may be conducted. The data provide compelling proof of concept for the application of DOT1L inhibitors for selective killing of MLL-rearranged leukemias and thus portent the utility of DOT1L inhibitors for therapeutic intervention in this disease.

Example 3

Tumor Anti-Proliferation Assays

The enzymatic activity of the protein methyltransferase (PMT) DOT1L has been shown to be a driver of cell proliferation in MLL-rearranged leukemia. Structure-guided design, together with robust biochemical and biological assays, was used to optimize the potency, selectivity and pharmacological features of the aminonucleosides, resulting in the Compound A2.

Compound A2 is a S-adenosyl methionine (SAM) competitive inhibitor of DOT11L that displays a K_i value of 80 μM and a drug-target residence time of >24 hours. The compound is highly selective for DOT1L, demonstrating >37,000-fold selectivity against all other PMTs tested. Crystallographic studies reveal that the high affinity, durable inhibition of DOT1L by Compound A2 has its origin in a conformational adaptation of the protein that attends inhibitor binding, extending the compound binding pocket to include novel recognition elements beyond the SAM binding active site, as illustrated in FIG. 6. Treatment of leukemia cells with Compound A2 results in concentration- and time-dependent diminution of H3K79 methylation without effect on the methylation status of other histone sites. The diminution of H3K79 methylation leads to inhibition of key MLL target genes and selective, apoptotic cell killing in MLL-rearranged leukemia cells, but has minimal impact on non-rearranged cells. Compound A2 is highly soluble in aqueous solution and can thus be formulated for intravenous administration. The effective pharmacokinetic half-life of Compound A2 in systemic circulation has been measured to be 0.25 and 1.5 h in rats and dogs, respectively. A nude rat subcutaneous xenograft model of MLL-rearranged leukemia has been established.

Four groups of 10 (Groups 1, 2, 3, and 4 female RH nu/nu rats (7 weeks old, weighing 120-160 g) bearing MV4-11 xenograft tumors of sizes ranging from 300-600 mm³ were implanted with a catheter in the femoral vein). The infusion flow rate was set at 1,500 μL/hour/kg and was adjusted to the most recent mean body weight of each treatment group (as an example, the infusion flow rate was 300 μL/hour for a group of rats having a mean body weight of 200 g). Group 1 received vehicle via a 21-day continuous IV infusion. Group 2 received 21-day continuous IV infusion of the test substance at 35 mg/kg/day. Group 3 received a daily 8-hour continuous IV infusion of the test substance at 67 mg/kg/day for 21 consecutive days. Between two IV infusions of the test substance, the rats were kept under IV infusion with NaCl 0.9% solution. Group 4 received a 21-day continuous IV infusion of the test substance at 70 mg/kg/day. Syringes used for the IV infusion were replaced every day.

Blood samples were taken from all animals in Groups 1, 2, and 4 on designated days and assayed for plasma levels of Compound A2. Tumor size was measured on the designated days as shown in FIG. 1. The rats were terminated when the subcutaneous tumor reached a maximum volume of 9,000 mm³ or at a maximum of 55 days after tumor cells injection.

As shown in FIG. 1, continuous intravenous infusion of Compound A2 for 21 days in this model leads to dose-dependent anti-tumor activity. At the highest dose, complete tumor regressions are achieved with no regrowth for up to 32 days after the cessation of treatment. In FIG. 1, Dose 1=35 mg/kg/day, and Dose 2=70 mg/kg/day.

No significant weight loss or obvious toxicity was observed in rats treated with Compound A2 during this efficacy study. Compound A2 is thus a potent, selective inhibitor of DOT1L that demonstrates strong efficacy in a rat xenograft model of MLL-rearranged leukemia.

TABLE 7
Summary of the Diffraction Data, Refinement, and Structure Statistics for Crystal Structures
	Compound C1	Compound C118	Compound D16
Diffraction Data
Resolution (Å)*	25.00-2.50	(2.59-2.50)	1.70-2.80	(2.95-2.80)	50.00-2.85	(2.95-2.85)
Space group	P65	P65	P65
Unit-cell parameters
a (Å)	152.81	157.60	155.05
b (Å)	152.81	157.60	155.05
c (Å)	51.37	49.15	48.45
α (°)	90.00	90.00	90
β (°)	90.00	90.00	90
γ (°)	120.00	120.00	90
Completemess (%)*	96.7	(81.3)	100.0	(99.9)	99.8	(100.0)
Redundancy*	11.5	(3.1)	6.1	(5.9)	5.6	(5.6)
Average I/σI*	20.5	(2.41)	11.8	(3.5)	23.1	(4.0)
Rmerge (%)*	9.5	(39.0)	9.4	(42.1)	8.0	(53.9)
Refinement Statistics
Data (no cutoff) (Å)*	23.94-2.50	(2.56-2.50)	0.00-2.80	(2.87-2.80)	41.09-2.85	(2.92-2.85)
Rworking (%)/No. of reflections*	20.8/20874	(40.0/1274)	21.0/15726	(30.0/1149)	20.9/14244	(27.0/974)
Rfree (%)/No. of reflections*	26.3/1189	(37.8/58)	26.1/886	(40.2/54)	26.2/785	(40.6/61)
R.m.s.d in bond lengths (Å)	0.01	0.009	0.009
R.m.s.d in bond angles (°)	1.334	1.291	1.46
Mean B factors (Å2)	58.98	74.06	90.38
Mean B factors for ligand (Å2)	44.47	61.82	75.23
Ramachandran plot
Favored (%)	90.3	87.2	87.5
Additionally allowed (%)	9.7	12.8	12.5
Generously allowed (%)	0	0	0
*Values in parentheses are for the highest-resolution shell
indicates data missing or illegible when filed

The entire disclosure of each of the patent documents and scientific articles referred to herein is incorporated by reference for all purposes.

The invention can be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting on the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.

APPENDIX

TABLE S1
TITLE	CRYSTAL STRUCTURE OF DOT1L IN COMPLEX WITH EPZ004777
CRYST1	155.053 155.053  48.452  90.00 90.00 120.00 P 65      6
ORIGX1	1.000000  0.000000  0.000000     0.00000
ORIGX2	0.000000  1.000000  0.000000     0.00000
ORIGX3	0.000000  0.000000  1.000000     0.00000
SCALE1	0.006449  0.003724  0.000000     0.00000
SCALE2	0.000000  0.007447  0.000000     0.00000
SCALE3	0.000000  0.000000  0.020639     0.00000
ATOM	1	N	LYS	A	4	11.559	73.167	16.864	1.00	122.46	N
ATOM	2	CA	LYS	A	4	11.526	74.573	16.363	1.00	123.45	C
ATOM	3	C	LYS	A	4	11.676	74.613	14.840	1.00	120.69	C
ATOM	4	O	LYS	A	4	11.076	73.796	14.130	1.00	118.19	O
ATOM	5	CB	LYS	A	4	12.609	75.407	17.039	1.00	121.78	C
ATOM	6	N	LEU	A	5	12.469	75.570	14.357	1.00	110.48	N
ATOM	7	CA	LEU	A	5	12.773	75.726	12.933	1.00	107.29	C
ATOM	8	C	LEU	A	5	13.516	74.517	12.321	1.00	103.99	C
ATOM	9	O	LEU	A	5	14.355	73.895	12.979	1.00	109.08	O
ATOM	10	CB	LEU	A	5	13.559	77.023	12.726	1.00	105.89	C
ATOM	11	CG	LEU	A	5	12.755	78.283	12.343	1.00	107.16	C
ATOM	12	CD1	LEU	A	5	11.305	78.230	12.811	1.00	96.94	C
ATOM	13	CD2	LEU	A	5	13.442	79.576	12.785	1.00	92.46	C
ATOM	14	N	GLU	A	6	13.186	74.189	11.070	1.00	90.61	N
ATOM	15	CA	GLU	A	6	13.716	73.000	10.375	1.00	83.94	C
ATOM	16	C	GLU	A	6	13.901	73.228	8.876	1.00	90.90	C
ATOM	17	O	GLU	A	6	13.280	74.123	8.284	1.00	93.50	O
ATOM	18	CB	GLU	A	6	12.785	71.798	10.537	1.00	71.55	C
ATOM	19	CG	GLU	A	6	12.892	71.058	11.854	1.00	76.84	C
ATOM	20	CD	GLU	A	6	12.192	69.698	11.823	1.00	86.30	C
ATOM	21	OE1	GLU	A	6	12.448	68.900	12.754	1.00	87.72	O
ATOM	22	OE2	GLU	A	6	11.397	69.407	10.881	1.00	79.35	O
ATOM	23	N	LEU	A	7	14.766	72.420	8.266	1.00	87.34	N
ATOM	24	CA	LEU	A	7	14.727	72.216	6.816	1.00	81.97	C
ATOM	25	C	LEU	A	7	14.592	70.711	6.568	1.00	77.11	C
ATOM	26	O	LEU	A	7	15.086	69.898	7.362	1.00	75.10	O
ATOM	27	CB	LEU	A	7	15.944	72.830	6.118	1.00	77.48	C
ATOM	28	CG	LEU	A	7	16.065	74.364	6.193	1.00	82.84	C
ATOM	29	CD1	LEU	A	7	17.517	74.800	6.370	1.00	74.92	C
ATOM	30	CD2	LEU	A	7	15.429	75.084	5.002	1.00	81.08	C
ATOM	31	N	ARG	A	8	13.875	70.332	5.513	1.00	72.20	N
ATOM	32	CA	ARG	A	8	13.720	68.904	5.199	1.00	79.52	C
ATOM	33	C	ARG	A	8	13.992	68.659	3.729	1.00	84.44	C
ATOM	34	O	ARG	A	8	13.578	69.450	2.862	1.00	87.68	O
ATOM	35	CB	ARG	A	8	12.331	68.363	5.544	1.00	78.70	C
ATOM	36	CG	ARG	A	8	11.708	68.936	6.801	1.00	96.63	C
ATOM	37	CD	ARG	A	8	10.194	68.764	6.789	1.00	100.99	C
ATOM	38	NE	ARG	A	8	9.827	67.358	6.952	1.00	104.07	N
ATOM	39	CZ	ARG	A	8	9.876	66.706	8.112	1.00	101.52	C
ATOM	40	NH1	ARG	A	8	10.279	67.337	9.220	1.00	92.27	N
ATOM	41	NH2	ARG	A	8	9.528	65.420	8.164	1.00	93.27	N
ATOM	42	N	LEU	A	9	14.700	67.569	3.445	1.00	79.34	N
ATOM	43	CA	LEU	A	9	14.893	67.177	2.061	1.00	77.44	C
ATOM	44	C	LEU	A	9	14.243	65.831	1.805	1.00	73.97	C
ATOM	45	O	LEU	A	9	14.486	64.862	2.533	1.00	66.03	O
ATOM	46	CB	LEU	A	9	16.377	67.160	1.695	1.00	79.05	C
ATOM	47	CG	LEU	A	9	17.170	68.464	1.637	1.00	74.03	C
ATOM	48	CD1	LEU	A	9	18.539	68.155	1.059	1.00	81.81	C
ATOM	49	CD2	LEU	A	9	16.481	69.527	0.793	1.00	77.52	C
ATOM	50	N	LYS	A	10	13.399	65.798	0.781	1.00	67.19	N
ATOM	51	CA	LYS	A	10	12.726	64.588	0.389	1.00	73.14	C
ATOM	52	C	LYS	A	10	13.687	63.759	−0.435	1.00	69.65	C
ATOM	53	O	LYS	A	10	14.380	64.293	−1.299	1.00	71.70	O
ATOM	54	CB	LYS	A	10	11.477	64.915	−0.443	1.00	85.23	C
ATOM	55	CG	LYS	A	10	10.209	65.111	0.380	1.00	95.23	C
ATOM	56	CD	LYS	A	10	8.984	65.374	−0.489	1.00	96.06	C
ATOM	57	CE	LYS	A	10	7.707	65.234	0.327	1.00	95.75	C
ATOM	58	NZ	LYS	A	10	6.514	65.146	−0.551	1.00	90.22	N
ATOM	59	N	SER	A	11	13.718	62.457	−0.162	1.00	69.88	N
ATOM	60	CA	SER	A	11	14.516	61.499	−0.929	1.00	67.74	C
ATOM	61	C	SER	A	11	13.957	61.399	−2.323	1.00	71.29	C
ATOM	62	O	SER	A	11	12.751	61.474	−2.495	1.00	79.64	O
ATOM	63	CB	SER	A	11	14.487	60.118	−0.275	1.00	67.19	C
ATOM	64	OG	SER	A	11	14.472	59.109	−1.276	1.00	73.16	O
ATOM	65	N	PRO	A	12	14.824	61.233	−3.335	1.00	81.41	N
ATOM	66	CA	PRO	A	12	14.270	61.096	−4.687	1.00	75.72	C
ATOM	67	C	PRO	A	12	13.647	59.726	−4.912	1.00	68.44	C
ATOM	68	O	PRO	A	12	13.152	59.445	−5.994	1.00	74.54	O
ATOM	69	CB	PRO	A	12	15.501	61.288	−5.590	1.00	71.93	C
ATOM	70	CG	PRO	A	12	16.656	60.875	−4.736	1.00	70.99	C
ATOM	71	CD	PRO	A	12	16.293	61.365	−3.359	1.00	77.59	C
ATOM	72	N	VAL	A	13	13.687	58.857	−3.918	1.00	66.66	N
ATOM	73	CA	VAL	A	13	13.053	57.548	−4.096	1.00	74.16	C
ATOM	74	C	VAL	A	13	12.102	57.197	−2.939	1.00	80.07	C
ATOM	75	O	VAL	A	13	11.876	56.021	−2.623	1.00	84.87	O
ATOM	76	CB	VAL	A	13	14.084	56.425	−4.400	1.00	68.30	C
ATOM	77	CG1	VAL	A	13	14.809	56.730	−5.695	1.00	57.60	C
ATOM	78	CG2	VAL	A	13	15.077	56.245	−3.256	1.00	64.65	C
ATOM	79	N	GLY	A	14	11.557	58.237	−2.315	1.00	73.70	N
ATOM	80	CA	GLY	A	14	10.546	58.087	−1.287	1.00	77.34	C
ATOM	81	C	GLY	A	14	10.996	57.506	0.035	1.00	77.29	C
ATOM	82	O	GLY	A	14	10.179	57.001	0.799	1.00	89.95	O
ATOM	83	N	ALA	A	15	12.287	57.570	0.324	1.00	78.96	N
ATOM	84	CA	ALA	A	15	12.765	57.156	1.638	1.00	76.62	C
ATOM	85	C	ALA	A	15	12.453	58.274	2.624	1.00	74.68	C
ATOM	86	O	ALA	A	15	12.060	59.376	2.210	1.00	79.35	O
ATOM	87	CB	ALA	A	15	14.253	56.865	1.595	1.00	72.42	C
ATOM	88	N	GLU	A	16	12.628	58.007	3.917	1.00	69.70	N
ATOM	89	CA	GLU	A	16	12.357	59.031	4.930	1.00	78.77	C
ATOM	90	C	GLU	A	16	13.112	60.329	4.600	1.00	77.36	C
ATOM	91	O	GLU	A	16	14.304	60.295	4.324	1.00	85.69	O
ATOM	92	CB	GLU	A	16	12.686	58.508	6.336	1.00	83.56	C
ATOM	93	CG	GLU	A	16	12.219	57.071	6.602	1.00	89.72	C
ATOM	94	CD	GLU	A	16	10.715	56.877	6.397	0.50	89.31	C
ATOM	95	OE1	GLU	A	16	10.314	55.876	5.760	0.50	85.58	O
ATOM	96	OE2	GLU	A	16	9.929	57.733	6.860	0.50	88.97	O
ATOM	97	N	PRO	A	17	12.415	61.476	4.584	1.00	83.00	N
ATOM	98	CA	PRO	A	17	13.119	62.719	4.263	1.00	81.80	C
ATOM	99	C	PRO	A	17	14.239	62.980	5.251	1.00	78.20	C
ATOM	100	O	PRO	A	17	14.241	62.427	6.350	1.00	76.63	O
ATOM	101	CB	PRO	A	17	12.035	63.793	4.424	1.00	77.75	C
ATOM	102	CG	PRO	A	17	11.094	63.198	5.407	1.00	79.83	C
ATOM	103	CD	PRO	A	17	11.040	61.740	5.032	1.00	79.58	C
ATOM	104	N	ALA	A	18	15.197	63.801	4.849	1.00	82.40	N
ATOM	105	CA	ALA	A	18	16.310	64.127	5.712	1.00	73.01	C
ATOM	106	C	ALA	A	18	15.956	65.429	6.388	1.00	77.58	C
ATOM	107	O	ALA	A	18	15.526	66.391	5.735	1.00	78.01	O
ATOM	108	CB	ALA	A	18	17.590	64.253	4.908	1.00	63.80	C
ATOM	109	N	VAL	A	19	16.128	65.443	7.704	1.00	81.32	N
ATOM	110	CA	VAL	A	19	15.692	66.549	8.541	1.00	82.88	C
ATOM	111	C	VAL	A	19	16.888	67.234	9.225	1.00	80.35	C
ATOM	112	O	VAL	A	19	17.589	66.606	10.009	1.00	79.38	O
ATOM	113	CB	VAL	A	19	14.690	66.050	9.623	1.00	79.17	C
ATOM	114	CG1	VAL	A	19	14.080	67.224	10.361	1.00	77.31	C
ATOM	115	CG2	VAL	A	19	13.585	65.195	9.011	1.00	77.94	C
ATOM	116	N	TYR	A	20	17.084	68.522	8.953	1.00	78.22	N
ATOM	117	CA	TYR	A	20	18.121	69.333	9.607	1.00	81.75	C
ATOM	118	C	TYR	A	20	17.576	70.389	10.595	1.00	89.01	C
ATOM	119	O	TYR	A	20	16.591	71.064	10.292	1.00	100.79	O
ATOM	120	CB	TYR	A	20	18.940	70.073	8.539	1.00	85.08	C
ATOM	121	CG	TYR	A	20	19.620	69.171	7.536	1.00	89.38	C
ATOM	122	CD1	TYR	A	20	18.956	68.745	6.385	1.00	82.61	C
ATOM	123	CD2	TYR	A	20	20.936	68.734	7.743	1.00	83.99	C
ATOM	124	CE1	TYR	A	20	19.581	67.903	5.478	1.00	81.71	C
ATOM	125	CE2	TYR	A	20	21.567	67.900	6.831	1.00	76.12	C
ATOM	126	CZ	TYR	A	20	20.889	67.493	5.704	1.00	76.29	C
ATOM	127	OH	TYR	A	20	21.514	66.671	4.807	1.00	71.44	O
ATOM	128	N	PRO	A	21	18.238	70.571	11.758	1.00	89.31	N
ATOM	129	CA	PRO	A	21	17.917	71.694	12.631	1.00	83.01	C
ATOM	130	C	PRO	A	21	18.389	73.018	12.056	1.00	88.41	C
ATOM	131	O	PRO	A	21	19.400	73.063	11.341	1.00	87.98	O
ATOM	132	CB	PRO	A	21	18.751	71.405	13.873	1.00	81.22	C
ATOM	133	CG	PRO	A	21	19.928	70.673	13.341	1.00	85.34	C
ATOM	134	CD	PRO	A	21	19.316	69.748	12.336	1.00	93.55	C
ATOM	135	N	TRP	A	22	17.664	74.088	12.379	1.00	87.01	N
ATOM	136	CA	TRP	A	22	18.176	75.439	12.193	1.00	82.10	C
ATOM	137	C	TRP	A	22	18.450	76.100	13.530	1.00	90.64	C
ATOM	138	O	TRP	A	22	17.729	75.843	14.489	1.00	94.14	O
ATOM	139	CB	TRP	A	22	17.228	76.256	11.369	1.00	73.52	C
ATOM	140	CG	TRP	A	22	17.798	77.596	11.047	1.00	75.17	C
ATOM	141	CD1	TRP	A	22	17.853	78.703	11.878	1.00	76.94	C
ATOM	142	CD2	TRP	A	22	18.443	78.025	9.789	1.00	76.24	C
ATOM	143	NE1	TRP	A	22	18.459	79.761	11.239	1.00	86.44	N
ATOM	144	CE2	TRP	A	22	18.839	79.423	9.990	1.00	77.46	C
ATOM	145	CE3	TRP	A	22	18.717	77.416	8.568	1.00	74.98	C
ATOM	146	CZ2	TRP	A	22	19.476	80.162	8.998	1.00	78.22	C
ATOM	147	CZ3	TRP	A	22	19.364	78.172	7.573	1.00	75.79	C
ATOM	148	CH2	TRP	A	22	19.734	79.512	7.787	1.00	77.10	C
ATOM	149	N	PRO	A	23	19.550	76.887	13.644	1.00	92.30	N
ATOM	150	CA	PRO	A	23	20.591	77.080	12.632	1.00	86.39	C
ATOM	151	C	PRO	A	23	21.282	75.761	12.374	1.00	81.09	C
ATOM	152	O	PRO	A	23	21.382	74.906	13.280	1.00	80.65	O
ATOM	153	CB	PRO	A	23	21.547	78.085	13.276	1.00	88.59	C
ATOM	154	CG	PRO	A	23	21.388	77.861	14.734	1.00	96.33	C
ATOM	155	CD	PRO	A	23	19.941	77.480	14.936	1.00	97.81	C
ATOM	156	N	LEU	A	24	21.702	75.596	11.126	1.00	74.42	N
ATOM	157	CA	LEU	A	24	22.324	74.372	10.660	1.00	69.83	C
ATOM	158	C	LEU	A	24	23.739	74.217	11.232	1.00	71.45	C
ATOM	159	O	LEU	A	24	24.557	75.146	11.134	1.00	62.32	O
ATOM	160	CB	LEU	A	24	22.415	74.430	9.160	1.00	66.08	C
ATOM	161	CG	LEU	A	24	21.135	74.674	8.402	1.00	56.89	C
ATOM	162	CD1	LEU	A	24	21.557	75.296	7.089	1.00	53.00	C
ATOM	163	CD2	LEU	A	24	20.455	73.333	8.206	1.00	54.20	C
ATOM	164	N	PRO	A	25	24.036	73.038	11.812	1.00	70.59	N
ATOM	165	CA	PRO	A	25	25.338	72.803	12.442	1.00	71.75	C
ATOM	166	C	PRO	A	25	26.505	73.023	11.493	1.00	70.36	C
ATOM	167	O	PRO	A	25	26.368	72.922	10.258	1.00	68.18	O
ATOM	168	CB	PRO	A	25	25.280	71.321	12.833	1.00	71.82	C
ATOM	169	CG	PRO	A	25	23.827	70.999	12.902	1.00	72.55	C
ATOM	170	CD	PRO	A	25	23.212	71.819	11.804	1.00	68.44	C
ATOM	171	N	VAL	A	26	27.647	73.346	12.075	1.00	69.89	N
ATOM	172	CA	VAL	A	26	28.908	73.277	11.335	1.00	72.95	C
ATOM	173	C	VAL	A	26	29.654	72.047	11.846	1.00	68.76	C
ATOM	174	O	VAL	A	26	29.553	71.699	13.039	1.00	65.86	O
ATOM	175	CB	VAL	A	26	29.739	74.585	11.417	1.00	71.15	C
ATOM	176	CG1	VAL	A	26	29.277	75.444	12.565	1.00	76.50	C
ATOM	177	CG2	VAL	A	26	31.219	74.297	11.577	1.00	76.25	C
ATOM	178	N	TYR	A	27	30.350	71.364	10.935	1.00	70.07	N
ATOM	179	CA	TYR	A	27	31.046	70.096	11.266	1.00	72.10	C
ATOM	180	C	TYR	A	27	32.522	70.302	11.658	1.00	73.43	C
ATOM	181	O	TYR	A	27	32.999	69.723	12.642	1.00	69.33	O
ATOM	182	CB	TYR	A	27	30.933	69.109	10.103	1.00	63.02	C
ATOM	183	CG	TYR	A	27	29.505	68.722	9.778	1.00	64.65	C
ATOM	184	CD1	TYR	A	27	28.684	68.128	10.741	1.00	61.52	C
ATOM	185	CD2	TYR	A	27	28.967	68.968	8.511	1.00	62.95	C
ATOM	186	CE1	TYR	A	27	27.390	67.762	10.441	1.00	62.08	C
ATOM	187	CE2	TYR	A	27	27.667	68.620	8.205	1.00	57.70	C
ATOM	188	CZ	TYR	A	27	26.883	68.018	9.167	1.00	65.81	C
ATOM	189	OH	TYR	A	27	25.576	67.664	8.869	1.00	74.91	O
ATOM	190	N	ASP	A	28	33.199	71.154	10.886	1.00	67.07	N
ATOM	191	CA	ASP	A	28	34.616	71.451	10.988	1.00	69.15	C
ATOM	192	C	ASP	A	28	34.826	72.730	10.178	1.00	73.67	C
ATOM	193	O	ASP	A	28	33.869	73.246	9.578	1.00	73.43	O
ATOM	194	CB	ASP	A	28	35.460	70.303	10.412	1.00	66.90	C
ATOM	195	CG	ASP	A	28	35.355	70.180	8.892	1.00	73.46	C
ATOM	196	OD1	ASP	A	28	35.442	71.209	8.174	1.00	68.45	O
ATOM	197	OD2	ASP	A	28	35.213	69.030	8.403	1.00	77.17	O
ATOM	198	N	LYS	A	29	36.062	73.220	10.127	1.00	69.48	N
ATOM	199	CA	LYS	A	29	36.349	74.516	9.514	1.00	72.24	C
ATOM	200	C	LYS	A	29	35.912	74.598	8.053	1.00	75.98	C
ATOM	201	O	LYS	A	29	35.663	75.688	7.555	1.00	86.69	O
ATOM	202	CB	LYS	A	29	37.841	74.875	9.666	1.00	89.07	C
ATOM	203	CG	LYS	A	29	38.201	76.338	9.413	1.00	90.87	C
ATOM	204	CD	LYS	A	29	39.710	76.578	9.397	1.00	99.60	C
ATOM	205	CE	LYS	A	29	40.021	78.069	9.273	1.00	102.22	C
ATOM	206	NZ	LYS	A	29	41.411	78.378	8.826	1.00	105.11	N
ATOM	207	N	HIS	A	30	35.781	73.460	7.374	1.00	80.95	N
ATOM	208	CA	HIS	A	30	35.474	73.462	5.933	1.00	88.17	C
ATOM	209	C	HIS	A	30	34.225	72.700	5.549	1.00	84.97	C
ATOM	210	O	HIS	A	30	34.087	72.293	4.395	1.00	82.53	O
ATOM	211	CB	HIS	A	30	36.667	72.918	5.133	1.00	102.37	C
ATOM	212	CG	HIS	A	30	38.013	73.462	5.577	1.00	110.35	C
ATOM	213	ND1	HIS	A	30	38.517	74.626	5.111	1.00	107.23	N
ATOM	214	CD2	HIS	A	30	38.960	72.949	6.471	1.00	109.01	C
ATOM	215	CE1	HIS	A	30	39.718	74.852	5.683	1.00	118.08	C
ATOM	216	NE2	HIS	A	30	39.987	73.824	6.514	1.00	119.99	N
ATOM	217	N	HIS	A	31	33.322	72.474	6.506	1.00	79.71	N
ATOM	218	CA	HIS	A	31	32.082	71.721	6.271	1.00	75.39	C
ATOM	219	C	HIS	A	31	31.004	72.081	7.243	1.00	75.51	C
ATOM	220	O	HIS	A	31	31.222	72.069	8.464	1.00	72.11	O
ATOM	221	CB	HIS	A	31	32.319	70.216	6.378	1.00	79.56	C
ATOM	222	CG	HIS	A	31	33.460	69.721	5.534	1.00	87.23	C
ATOM	223	ND1	HIS	A	31	34.747	69.927	5.868	1.00	84.08	N
ATOM	224	CD2	HIS	A	31	33.473	69.029	4.334	1.00	82.25	C
ATOM	225	CE1	HIS	A	31	35.538	69.394	4.934	1.00	87.77	C
ATOM	226	NE2	HIS	A	31	34.760	68.841	3.997	1.00	81.02	N
ATOM	227	N	ASP	A	32	29.819	72.372	6.718	1.00	70.47	N
ATOM	228	CA	ASP	A	32	28.646	72.583	7.559	1.00	71.27	C
ATOM	229	C	ASP	A	32	27.436	71.965	6.912	1.00	64.40	C
ATOM	230	O	ASP	A	32	27.497	71.562	5.757	1.00	61.62	O
ATOM	231	CB	ASP	A	32	28.405	74.078	7.787	1.00	71.19	C
ATOM	232	CG	ASP	A	32	28.338	74.865	6.501	1.00	73.26	C
ATOM	233	OD1	ASP	A	32	27.909	74.327	5.465	1.00	79.48	O
ATOM	234	OD2	ASP	A	32	28.707	76.049	6.526	1.00	83.84	O
ATOM	235	N	ALA	A	33	26.321	71.928	7.635	1.00	67.27	N
ATOM	236	CA	ALA	A	33	25.085	71.374	7.069	1.00	62.24	C
ATOM	237	C	ALA	A	33	24.494	72.212	5.917	1.00	63.41	C
ATOM	238	O	ALA	A	33	23.940	71.661	4.956	1.00	64.01	O
ATOM	239	CB	ALA	A	33	24.072	71.125	8.148	1.00	50.07	C
ATOM	240	N	ALA	A	34	24.627	73.534	5.986	1.00	61.47	N
ATOM	241	CA	ALA	A	34	24.161	74.355	4.878	1.00	61.33	C
ATOM	242	C	ALA	A	34	24.654	73.767	3.571	1.00	67.56	C
ATOM	243	O	ALA	A	34	23.849	73.473	2.661	1.00	73.17	O
ATOM	244	CB	ALA	A	34	24.630	75.787	5.014	1.00	58.78	C
ATOM	245	N	HIS	A	35	25.971	73.568	3.479	1.00	69.69	N
ATOM	246	CA	HIS	A	35	26.568	73.129	2.213	1.00	63.66	C
ATOM	247	C	HIS	A	35	26.293	71.691	1.924	1.00	56.08	C
ATOM	248	O	HIS	A	35	26.099	71.334	0.760	1.00	53.02	O
ATOM	249	CB	HIS	A	35	28.035	73.499	2.113	1.00	71.29	C
ATOM	250	CG	HIS	A	35	28.268	74.992	2.062	1.00	80.72	C
ATOM	251	ND1	HIS	A	35	28.230	75.772	3.167	1.00	82.07	N
ATOM	252	CD2	HIS	A	35	28.535	75.842	0.987	1.00	80.45	C
ATOM	253	CE1	HIS	A	35	28.462	77.053	2.816	1.00	87.35	C
ATOM	254	NE2	HIS	A	35	28.641	77.094	1.480	1.00	82.51	N
ATOM	255	N	GLU	A	36	26.189	70.865	2.963	1.00	47.05	N
ATOM	256	CA	GLU	A	36	25.667	69.507	2.771	1.00	51.19	C
ATOM	257	C	GLU	A	36	24.325	69.578	2.009	1.00	61.53	C
ATOM	258	O	GLU	A	36	24.102	68.819	1.031	1.00	59.78	O
ATOM	259	CB	GLU	A	36	25.472	68.791	4.117	1.00	47.97	C
ATOM	260	CG	GLU	A	36	25.076	67.319	4.018	1.00	52.48	C
ATOM	261	CD	GLU	A	36	24.919	66.640	5.387	1.00	63.88	C
ATOM	262	OE1	GLU	A	36	25.625	67.023	6.346	1.00	73.74	O
ATOM	263	OE2	GLU	A	36	24.076	65.724	5.532	1.00	64.59	O
ATOM	264	N	ILE	A	37	23.451	70.504	2.445	1.00	58.25	N
ATOM	265	CA	ILE	A	37	22.115	70.621	1.882	1.00	56.95	C
ATOM	266	C	ILE	A	37	22.208	70.988	0.414	1.00	59.53	C
ATOM	267	O	ILE	A	37	21.659	70.289	−0.448	1.00	62.54	O
ATOM	268	CB	ILE	A	37	21.253	71.605	2.675	1.00	56.86	C
ATOM	269	CG1	ILE	A	37	20.604	70.896	3.858	1.00	59.71	C
ATOM	270	CG2	ILE	A	37	20.149	72.159	1.821	1.00	55.03	C
ATOM	271	CD1	ILE	A	37	20.294	71.799	5.030	1.00	53.48	C
ATOM	272	N	ILE	A	38	22.942	72.049	0.130	1.00	55.45	N
ATOM	273	CA	ILE	A	38	23.128	72.477	−1.248	1.00	62.73	C
ATOM	274	C	ILE	A	38	23.741	71.404	−2.125	1.00	62.25	C
ATOM	275	O	ILE	A	38	23.317	71.181	−3.269	1.00	62.70	O
ATOM	276	CB	ILE	A	38	24.030	73.716	−1.310	1.00	68.78	C
ATOM	277	CG1	ILE	A	38	23.383	74.841	−0.488	1.00	64.29	C
ATOM	278	CG2	ILE	A	38	24.346	74.095	−2.761	1.00	57.22	C
ATOM	279	CD1	ILE	A	38	24.159	76.129	−0.518	1.00	68.97	C
ATOM	280	N	GLU	A	39	24.751	70.740	−1.590	1.00	69.88	N
ATOM	281	CA	GLU	A	39	25.476	69.751	−2.368	1.00	70.71	C
ATOM	282	C	GLU	A	39	24.569	68.571	−2.680	1.00	67.85	C
ATOM	283	O	GLU	A	39	24.570	68.069	−3.815	1.00	65.96	O
ATOM	284	CB	GLU	A	39	26.702	69.291	−1.610	1.00	79.61	C
ATOM	285	CG	GLU	A	39	27.971	69.389	−2.419	1.00	93.30	C
ATOM	286	CD	GLU	A	39	28.468	70.807	−2.468	1.00	104.34	C
ATOM	287	OE1	GLU	A	39	29.082	71.242	−1.455	1.00	105.63	O
ATOM	288	OE2	GLU	A	39	28.237	71.467	−3.515	1.00	103.58	O
ATOM	289	N	THR	A	40	23.774	68.156	−1.687	1.00	57.26	N
ATOM	290	CA	THR	A	40	22.807	67.089	−1.907	1.00	55.23	C
ATOM	291	C	THR	A	40	21.804	67.447	−3.008	1.00	57.35	C
ATOM	292	O	THR	A	40	21.558	66.660	−3.921	1.00	58.36	O
ATOM	293	CB	THR	A	40	22.038	66.748	−0.643	1.00	57.10	C
ATOM	294	OG1	THR	A	40	22.954	66.445	0.433	1.00	54.49	O
ATOM	295	CG2	THR	A	40	21.139	65.582	−0.930	1.00	50.19	C
ATOM	296	N	ILE	A	41	21.245	68.649	−2.941	1.00	57.83	N
ATOM	297	CA	ILE	A	41	20.336	69.080	−3.979	1.00	57.80	C
ATOM	298	C	ILE	A	41	21.012	68.968	−5.344	1.00	65.51	C
ATOM	299	O	ILE	A	41	20.441	68.396	−6.297	1.00	67.17	O
ATOM	300	CB	ILE	A	41	19.791	70.490	−3.705	1.00	60.56	C
ATOM	301	CG1	ILE	A	41	18.770	70.440	−2.547	1.00	65.58	C
ATOM	302	CG2	ILE	A	41	19.163	71.072	−4.961	1.00	58.32	C
ATOM	303	CD1	ILE	A	41	18.344	71.800	−2.009	1.00	58.69	C
ATOM	304	N	ARG	A	42	22.241	69.477	−5.439	1.00	71.84	N
ATOM	305	CA	ARG	A	42	22.942	69.462	−6.715	1.00	67.37	C
ATOM	306	C	ARG	A	42	23.156	68.042	−7.189	1.00	65.96	C
ATOM	307	O	ARG	A	42	22.913	67.743	−8.371	1.00	65.55	O
ATOM	308	CB	ARG	A	42	24.263	70.199	−6.622	1.00	82.71	C
ATOM	309	CG	ARG	A	42	24.236	71.612	−7.183	1.00	91.22	C
ATOM	310	CD	ARG	A	42	23.831	72.597	−6.112	1.00	101.12	C
ATOM	311	NE	ARG	A	42	24.116	73.987	−6.468	1.00	121.12	N
ATOM	312	CZ	ARG	A	42	25.313	74.560	−6.383	1.00	116.46	C
ATOM	313	NH1	ARG	A	42	25.439	75.839	−6.711	1.00	115.56	N
ATOM	314	NH2	ARG	A	42	26.376	73.864	−5.979	1.00	104.93	N
ATOM	315	N	TRP	A	43	23.557	67.157	−6.267	1.00	59.20	N
ATOM	316	CA	TRP	A	43	23.744	65.754	−6.631	1.00	63.08	C
ATOM	317	C	TRP	A	43	22.511	65.089	−7.125	1.00	73.03	C
ATOM	318	O	TRP	A	43	22.560	64.394	−8.154	1.00	73.53	O
ATOM	319	CB	TRP	A	43	24.473	64.937	−5.555	1.00	65.57	C
ATOM	320	CG	TRP	A	43	25.945	65.234	−5.690	1.00	66.23	C
ATOM	321	CD1	TRP	A	43	26.739	66.008	−4.857	1.00	63.43	C
ATOM	322	CD2	TRP	A	43	26.806	64.886	−6.822	1.00	58.94	C
ATOM	323	NE1	TRP	A	43	27.998	66.125	−5.369	1.00	61.08	N
ATOM	324	CE2	TRP	A	43	28.099	65.474	−6.544	1.00	57.84	C
ATOM	325	CE3	TRP	A	43	26.639	64.135	−7.984	1.00	62.14	C
ATOM	326	CZ2	TRP	A	43	29.170	65.318	−7.401	1.00	58.37	C
ATOM	327	CZ3	TRP	A	43	27.731	63.972	−8.837	1.00	57.49	C
ATOM	328	CH2	TRP	A	43	28.962	64.558	−8.552	1.00	55.92	C
ATOM	329	N	VAL	A	44	21.380	65.326	−6.451	1.00	73.53	N
ATOM	330	CA	VAL	A	44	20.126	64.746	−6.919	1.00	69.07	C
ATOM	331	C	VAL	A	44	19.735	65.234	−8.323	1.00	66.53	C
ATOM	332	O	VAL	A	44	19.263	64.435	−9.152	1.00	64.21	O
ATOM	333	CB	VAL	A	44	18.994	64.886	−5.909	1.00	74.63	C
ATOM	334	CG1	VAL	A	44	17.733	64.249	−6.472	1.00	73.99	C
ATOM	335	CG2	VAL	A	44	19.386	64.204	−4.605	1.00	74.06	C
ATOM	336	N	CYS	A	45	19.983	66.504	−8.633	1.00	57.28	N
ATOM	337	CA	CYS	A	45	19.795	66.914	−10.028	1.00	63.19	C
ATOM	338	C	CYS	A	45	20.654	66.132	−11.026	1.00	70.69	C
ATOM	339	O	CYS	A	45	20.277	66.041	−12.185	1.00	82.95	O
ATOM	340	CB	CYS	A	45	19.953	68.415	−10.219	1.00	64.68	C
ATOM	341	SG	CYS	A	45	18.984	69.366	−9.019	1.00	75.91	S
ATOM	342	N	GLU	A	46	21.791	65.569	−10.603	1.00	73.56	N
ATOM	343	CA	GLU	A	46	22.610	64.769	−11.537	1.00	72.24	C
ATOM	344	C	GLU	A	46	22.056	63.386	−11.703	1.00	73.66	C
ATOM	345	O	GLU	A	46	22.240	62.774	−12.756	1.00	83.16	O
ATOM	346	CB	GLU	A	46	24.086	64.637	−11.127	1.00	75.63	C
ATOM	347	CG	GLU	A	46	24.852	65.933	−10.959	1.00	79.40	C
ATOM	348	CD	GLU	A	46	24.901	66.766	−12.221	1.00	83.95	C
ATOM	349	OE1	GLU	A	46	25.162	66.203	−13.313	1.00	81.43	O
ATOM	350	OE2	GLU	A	46	24.690	67.994	−12.102	1.00	90.40	O
ATOM	351	N	GLU	A	47	21.421	62.857	−10.661	1.00	70.52	N
ATOM	352	CA	GLU	A	47	20.780	61.553	−10.803	1.00	74.85	C
ATOM	353	C	GLU	A	47	19.608	61.688	−11.765	1.00	79.90	C
ATOM	354	O	GLU	A	47	19.370	60.818	−12.592	1.00	88.55	O
ATOM	355	CB	GLU	A	47	20.232	61.032	−9.480	1.00	77.96	C
ATOM	356	CG	GLU	A	47	21.212	60.895	−8.331	1.00	76.05	C
ATOM	357	CD	GLU	A	47	20.618	60.055	−7.208	1.00	77.04	C
ATOM	358	OE1	GLU	A	47	20.224	60.591	−6.148	1.00	80.59	O
ATOM	359	OE2	GLU	A	47	20.517	58.836	−7.391	1.00	81.05	O
ATOM	360	N	ILE	A	48	18.872	62.787	−11.647	1.00	79.18	N
ATOM	361	CA	ILE	A	48	17.650	62.931	−12.394	1.00	76.42	C
ATOM	362	C	ILE	A	48	17.727	64.167	−13.274	1.00	84.13	C
ATOM	363	O	ILE	A	48	17.429	65.291	−12.836	1.00	85.83	O
ATOM	364	CB	ILE	A	48	16.416	62.947	−11.472	1.00	76.61	C
ATOM	365	CG1	ILE	A	48	16.433	61.725	−10.566	1.00	77.66	C
ATOM	366	CG2	ILE	A	48	15.150	62.857	−12.297	1.00	87.70	C
ATOM	367	CD1	ILE	A	48	15.557	61.839	−9.344	1.00	77.11	C
ATOM	368	N	PRO	A	49	18.132	63.962	−14.534	1.00	82.54	N
ATOM	369	CA	PRO	A	49	18.185	65.052	−15.503	1.00	79.22	C
ATOM	370	C	PRO	A	49	16.894	65.867	−15.474	1.00	84.11	C
ATOM	371	O	PRO	A	49	16.931	67.099	−15.571	1.00	81.77	O
ATOM	372	CB	PRO	A	49	18.323	64.323	−16.840	1.00	78.41	C
ATOM	373	CG	PRO	A	49	18.955	63.003	−16.504	1.00	78.63	C
ATOM	374	CD	PRO	A	49	18.559	62.665	−15.097	1.00	78.84	C
ATOM	375	N	ASP	A	50	15.764	65.174	−15.328	1.00	90.72	N
ATOM	376	CA	ASP	A	50	14.444	65.815	−15.292	1.00	89.42	C
ATOM	377	C	ASP	A	50	14.304	66.821	−14.155	1.00	87.00	C
ATOM	378	O	ASP	A	50	13.857	67.955	−14.365	1.00	84.40	O
ATOM	379	CB	ASP	A	50	13.338	64.763	−15.227	1.00	99.33	C
ATOM	380	CG	ASP	A	50	12.892	64.285	−16.609	1.00	102.05	C
ATOM	381	OD1	ASP	A	50	13.165	64.987	−17.608	1.00	104.36	O
ATOM	382	OD2	ASP	A	50	12.257	63.208	−16.696	1.00	97.76	O
ATOM	383	N	LEU	A	51	14.714	66.418	−12.955	1.00	86.81	N
ATOM	384	CA	LEU	A	51	14.759	67.341	−11.816	1.00	82.70	C
ATOM	385	C	LEU	A	51	15.630	68.551	−12.127	1.00	81.31	C
ATOM	386	O	LEU	A	51	15.356	69.672	−11.700	1.00	76.65	O
ATOM	387	CB	LEU	A	51	15.317	66.629	−10.602	1.00	76.35	C
ATOM	388	CG	LEU	A	51	15.191	67.430	−9.323	1.00	80.32	C
ATOM	389	CD1	LEU	A	51	13.781	67.292	−8.787	1.00	83.45	C
ATOM	390	CD2	LEU	A	51	16.182	66.897	−8.305	1.00	82.46	C
ATOM	391	N	LYS	A	52	16.696	68.300	−12.877	1.00	87.09	N
ATOM	392	CA	LYS	A	52	17.619	69.342	−13.258	1.00	94.60	C
ATOM	393	C	LYS	A	52	16.851	70.365	−14.064	1.00	95.07	C
ATOM	394	O	LYS	A	52	16.966	71.573	−13.828	1.00	90.68	O
ATOM	395	CB	LYS	A	52	18.730	68.734	−14.099	1.00	104.05	C
ATOM	396	CG	LYS	A	52	19.996	69.553	−14.212	1.00	100.91	C
ATOM	397	CD	LYS	A	52	20.981	68.759	−15.037	1.00	102.41	C
ATOM	398	CE	LYS	A	52	22.366	68.838	−14.440	1.00	107.90	C
ATOM	399	NZ	LYS	A	52	23.204	67.750	−15.007	1.00	110.42	N
ATOM	400	N	LEU	A	53	16.048	69.865	−15.001	1.00	94.63	N
ATOM	401	CA	LEU	A	53	15.274	70.729	−15.878	1.00	93.67	C
ATOM	402	C	LEU	A	53	14.321	71.601	−15.070	1.00	93.74	C
ATOM	403	O	LEU	A	53	14.181	72.780	−15.359	1.00	98.19	O
ATOM	404	CB	LEU	A	53	14.539	69.917	−16.953	1.00	90.70	C
ATOM	405	CG	LEU	A	53	15.407	69.304	−18.065	1.00	104.24	C
ATOM	406	CD1	LEU	A	53	14.688	68.183	−18.816	1.00	101.19	C
ATOM	407	CD2	LEU	A	53	15.928	70.365	−19.039	1.00	94.60	C
ATOM	408	N	ALA	A	54	13.710	71.032	−14.031	1.00	91.95	N
ATOM	409	CA	ALA	A	54	12.753	71.770	−13.197	1.00	92.17	C
ATOM	410	C	ALA	A	54	13.373	72.903	−12.386	1.00	100.00	C
ATOM	411	O	ALA	A	54	12.656	73.758	−11.866	1.00	111.75	O
ATOM	412	CB	ALA	A	54	12.027	70.820	−12.258	1.00	83.09	C
ATOM	413	N	MET	A	55	14.695	72.914	−12.261	1.00	103.41	N
ATOM	414	CA	MET	A	55	15.318	73.797	−11.283	1.00	104.99	C
ATOM	415	C	MET	A	55	16.428	74.704	−11.792	1.00	112.02	C
ATOM	416	O	MET	A	55	17.322	75.071	−11.020	1.00	116.02	O
ATOM	417	CB	MET	A	55	15.856	72.967	−10.135	1.00	99.26	C
ATOM	418	CG	MET	A	55	14.793	72.228	−9.372	1.00	92.81	C
ATOM	419	SD	MET	A	55	15.538	71.706	−7.839	1.00	98.58	S
ATOM	420	CE	MET	A	55	15.406	73.181	−6.834	1.00	91.46	C
ATOM	421	N	GLU	A	56	16.369	75.086	−13.067	1.00	113.40	N
ATOM	422	CA	GLU	A	56	17.344	76.021	−13.633	1.00	117.21	C
ATOM	423	C	GLU	A	56	17.299	77.372	−12.911	1.00	120.50	C
ATOM	424	O	GLU	A	56	17.604	78.412	−13.491	1.00	130.81	O
ATOM	425	CB	GLU	A	56	17.112	76.187	−15.136	1.00	127.96	C
ATOM	426	CG	GLU	A	56	17.011	74.860	−15.879	1.00	141.64	C
ATOM	427	CD	GLU	A	56	17.109	75.003	−17.389	1.00	142.62	C
ATOM	428	OE1	GLU	A	56	16.057	74.904	−18.054	1.00	140.03	O
ATOM	429	OE2	GLU	A	56	18.230	75.207	−17.910	1.00	138.88	O
ATOM	430	N	ASN	A	57	16.903	77.324	−11.639	1.00	121.75	N
ATOM	431	CA	ASN	A	57	16.816	78.479	−10.749	1.00	126.58	C
ATOM	432	C	ASN	A	57	17.400	78.115	−9.370	1.00	129.88	C
ATOM	433	O	ASN	A	57	16.980	77.123	−8.761	1.00	117.68	O
ATOM	434	CB	ASN	A	57	15.354	78.935	−10.579	1.00	126.36	C
ATOM	435	CG	ASN	A	57	14.386	78.230	−11.527	1.00	129.24	C
ATOM	436	OD1	ASN	A	57	13.618	77.350	−11.109	1.00	123.56	O
ATOM	437	ND2	ASN	A	57	14.416	78.613	−12.809	1.00	117.82	N
ATOM	438	N	TYR	A	58	18.370	78.908	−8.899	1.00	136.08	N
ATOM	439	CA	TYR	A	58	18.910	78.811	−7.522	1.00	139.28	C
ATOM	440	C	TYR	A	58	19.772	80.021	−7.107	1.00	141.18	C
ATOM	441	O	TYR	A	58	20.918	80.195	−7.535	1.00	133.88	O
ATOM	442	CB	TYR	A	58	19.659	77.488	−7.287	1.00	139.24	C
ATOM	443	CG	TYR	A	58	20.882	77.319	−8.149	1.00	149.12	C
ATOM	444	CD1	TYR	A	58	22.161	77.428	−7.603	1.00	143.38	C
ATOM	445	CD2	TYR	A	58	20.759	77.069	−9.517	1.00	146.78	C
ATOM	446	CE1	TYR	A	58	23.280	77.288	−8.398	1.00	141.67	C
ATOM	447	CE2	TYR	A	58	21.871	76.932	−10.319	1.00	141.89	C
ATOM	448	CZ	TYR	A	58	23.126	77.037	−9.756	1.00	142.17	C
ATOM	449	OH	TYR	A	58	24.224	76.890	−10.564	1.00	140.68	O
ATOM	450	N	ASP	A	62	24.971	80.518	−6.604	1.00	126.07	N
ATOM	451	CA	ASP	A	62	25.035	81.417	−5.455	1.00	128.01	C
ATOM	452	C	ASP	A	62	23.700	81.495	−4.730	1.00	129.10	C
ATOM	453	O	ASP	A	62	22.635	81.411	−5.360	1.00	125.04	O
ATOM	454	CB	ASP	A	62	25.499	82.818	−5.867	1.00	132.09	C
ATOM	455	CG	ASP	A	62	26.984	83.051	−5.605	1.00	136.60	C
ATOM	456	OD1	ASP	A	62	27.498	84.107	−6.036	1.00	134.17	O
ATOM	457	OD2	ASP	A	62	27.634	82.191	−4.968	1.00	131.49	O
ATOM	458	N	TYR	A	63	23.779	81.670	−3.407	1.00	121.64	N
ATOM	459	CA	TYR	A	63	22.632	81.520	−2.515	1.00	117.94	C
ATOM	460	C	TYR	A	63	22.986	81.915	−1.088	1.00	114.45	C
ATOM	461	O	TYR	A	63	24.145	81.794	−0.695	1.00	119.70	O
ATOM	462	CB	TYR	A	63	22.176	80.065	−2.521	1.00	125.39	C
ATOM	463	CG	TYR	A	63	20.690	79.944	−2.554	1.00	136.22	C
ATOM	464	CD1	TYR	A	63	20.017	79.715	−3.755	1.00	142.39	C
ATOM	465	CD2	TYR	A	63	19.944	80.091	−1.393	1.00	142.75	C
ATOM	466	CE1	TYR	A	63	18.635	79.618	−3.792	1.00	149.23	C
ATOM	467	CE2	TYR	A	63	18.566	80.000	−1.417	1.00	150.31	C
ATOM	468	CZ	TYR	A	63	17.913	79.764	−2.611	1.00	154.31	C
ATOM	469	OH	TYR	A	63	16.538	79.676	−2.607	1.00	161.61	O
ATOM	470	N	ASP	A	64	21.999	82.356	−0.301	1.00	108.85	N
ATOM	471	CA	ASP	A	64	22.283	82.807	1.075	1.00	107.46	C
ATOM	472	C	ASP	A	64	21.971	81.808	2.176	1.00	105.51	C
ATOM	473	O	ASP	A	64	20.816	81.537	2.522	1.00	101.01	O
ATOM	474	CB	ASP	A	64	21.664	84.168	1.414	1.00	106.61	C
ATOM	475	CG	ASP	A	64	21.755	84.485	2.912	1.00	112.70	C
ATOM	476	OD1	ASP	A	64	22.850	84.822	3.401	1.00	105.14	O
ATOM	477	OD2	ASP	A	64	20.733	84.367	3.613	1.00	121.07	O
ATOM	478	N	THR	A	65	23.046	81.316	2.766	1.00	104.67	N
ATOM	479	CA	THR	A	65	23.002	80.150	3.620	1.00	100.34	C
ATOM	480	C	THR	A	65	22.802	80.519	5.087	1.00	98.44	C
ATOM	481	O	THR	A	65	22.643	79.641	5.952	1.00	93.97	O
ATOM	482	CB	THR	A	65	24.274	79.286	3.407	1.00	99.05	C
ATOM	483	OG1	THR	A	65	25.386	79.866	4.091	1.00	100.03	O
ATOM	484	CG2	THR	A	65	24.624	79.194	1.913	1.00	98.98	C
ATOM	485	N	LYS	A	66	22.810	81.821	5.372	1.00	107.87	N
ATOM	486	CA	LYS	A	66	22.603	82.269	6.748	1.00	114.46	C
ATOM	487	C	LYS	A	66	21.185	82.775	7.005	1.00	106.58	C
ATOM	488	O	LYS	A	66	20.767	82.864	8.158	1.00	104.42	O
ATOM	489	CB	LYS	A	66	23.683	83.262	7.217	1.00	114.35	C
ATOM	490	CG	LYS	A	66	23.903	83.276	8.741	1.00	130.48	C
ATOM	491	CD	LYS	A	66	24.839	82.177	9.270	1.00	130.50	C
ATOM	492	CE	LYS	A	66	24.139	80.848	9.581	1.00	126.24	C
ATOM	493	NZ	LYS	A	66	23.583	80.749	10.961	1.00	111.84	N
ATOM	494	N	SER	A	67	20.442	83.075	5.939	1.00	101.94	N
ATOM	495	CA	SER	A	67	19.020	83.380	6.084	1.00	107.41	C
ATOM	496	C	SER	A	67	18.193	82.125	5.946	1.00	96.08	C
ATOM	497	O	SER	A	67	18.203	81.490	4.896	1.00	97.48	O
ATOM	498	CB	SER	A	67	18.545	84.408	5.053	1.00	115.14	C
ATOM	499	OG	SER	A	67	17.156	84.662	5.207	1.00	119.22	O
ATOM	500	N	PHE	A	68	17.467	81.785	7.003	1.00	89.83	N
ATOM	501	CA	PHE	A	68	16.573	80.630	6.991	1.00	90.42	C
ATOM	502	C	PHE	A	68	15.548	80.694	5.860	1.00	97.62	C
ATOM	503	O	PHE	A	68	15.300	79.704	5.171	1.00	101.27	O
ATOM	504	CB	PHE	A	68	15.861	80.534	8.326	1.00	83.80	C
ATOM	505	CG	PHE	A	68	14.836	79.446	8.391	1.00	88.70	C
ATOM	506	CD1	PHE	A	68	14.926	78.455	9.357	1.00	95.02	C
ATOM	507	CD2	PHE	A	68	13.760	79.424	7.513	1.00	83.47	C
ATOM	508	CE1	PHE	A	68	13.970	77.453	9.433	1.00	99.19	C
ATOM	509	CE2	PHE	A	68	12.807	78.429	7.580	1.00	85.15	C
ATOM	510	CZ	PHE	A	68	12.903	77.445	8.546	1.00	96.44	C
ATOM	511	N	GLU	A	69	14.944	81.864	5.693	1.00	105.48	N
ATOM	512	CA	GLU	A	69	14.030	82.124	4.588	1.00	106.47	C
ATOM	513	C	GLU	A	69	14.681	81.792	3.242	1.00	97.73	C
ATOM	514	O	GLU	A	69	14.071	81.131	2.402	1.00	100.49	O
ATOM	515	CB	GLU	A	69	13.568	83.589	4.638	1.00	120.62	C
ATOM	516	CG	GLU	A	69	12.866	84.118	3.391	1.00	127.65	C
ATOM	517	CD	GLU	A	69	12.661	85.626	3.439	1.00	150.89	C
ATOM	518	OE1	GLU	A	69	11.520	86.079	3.202	1.00	163.68	O
ATOM	519	OE2	GLU	A	69	13.635	86.363	3.724	1.00	152.96	O
ATOM	520	N	SER	A	70	15.918	82.246	3.049	1.00	91.25	N
ATOM	521	CA	SER	A	70	16.651	81.978	1.815	1.00	84.80	C
ATOM	522	C	SER	A	70	16.944	80.480	1.648	1.00	91.08	C
ATOM	523	O	SER	A	70	16.812	79.944	0.548	1.00	91.69	O
ATOM	524	CB	SER	A	70	17.938	82.787	1.776	1.00	80.66	C
ATOM	525	OG	SER	A	70	18.656	82.517	0.588	1.00	79.86	O
ATOM	526	N	MET	A	71	17.317	79.810	2.740	1.00	88.99	N
ATOM	527	CA	MET	A	71	17.487	78.356	2.738	1.00	87.92	C
ATOM	528	C	MET	A	71	16.188	77.615	2.431	1.00	85.78	C
ATOM	529	O	MET	A	71	16.185	76.705	1.593	1.00	88.60	O
ATOM	530	CB	MET	A	71	18.096	77.833	4.061	1.00	93.69	C
ATOM	531	CG	MET	A	71	19.615	77.973	4.186	1.00	88.13	C
ATOM	532	SD	MET	A	71	20.553	77.476	2.716	1.00	88.52	S
ATOM	533	CE	MET	A	71	20.390	75.702	2.868	1.00	88.78	C
ATOM	534	N	GLN	A	72	15.092	78.004	3.088	1.00	82.82	N
ATOM	535	CA	GLN	A	72	13.821	77.284	2.910	1.00	81.80	C
ATOM	536	C	GLN	A	72	13.175	77.379	1.536	1.00	73.25	C
ATOM	537	O	GLN	A	72	12.512	76.447	1.115	1.00	74.61	O
ATOM	538	CB	GLN	A	72	12.801	77.625	3.973	1.00	80.12	C
ATOM	539	CG	GLN	A	72	11.702	76.582	4.029	1.00	85.60	C
ATOM	540	CD	GLN	A	72	10.848	76.722	5.269	1.00	96.93	C
ATOM	541	OE1	GLN	A	72	10.414	77.824	5.614	1.00	95.17	O
ATOM	542	NE2	GLN	A	72	10.604	75.604	5.953	1.00	93.88	N
ATOM	543	N	ARG	A	73	13.371	78.486	0.835	1.00	77.67	N
ATOM	544	CA	ARG	A	73	12.896	78.570	−0.538	1.00	91.82	C
ATOM	545	C	ARG	A	73	13.546	77.456	−1.322	1.00	89.42	C
ATOM	546	O	ARG	A	73	12.883	76.787	−2.126	1.00	91.85	O
ATOM	547	CB	ARG	A	73	13.230	79.916	−1.181	1.00	101.22	C
ATOM	548	CG	ARG	A	73	12.274	81.014	−0.785	1.00	113.69	C
ATOM	549	CD	ARG	A	73	12.564	82.306	−1.525	1.00	121.96	C
ATOM	550	NE	ARG	A	73	11.885	83.415	−0.861	1.00	137.41	N
ATOM	551	CZ	ARG	A	73	10.578	83.669	−0.951	1.00	145.86	C
ATOM	552	NH1	ARG	A	73	9.783	82.901	−1.692	1.00	142.04	N
ATOM	553	NH2	ARG	A	73	10.062	84.702	−0.296	1.00	147.81	N
ATOM	554	N	LEU	A	74	14.843	77.259	−1.062	1.00	86.56	N
ATOM	555	CA	LEU	A	74	15.642	76.250	−1.756	1.00	77.33	C
ATOM	556	C	LEU	A	74	15.135	74.846	−1.454	1.00	76.87	C
ATOM	557	O	LEU	A	74	14.871	74.068	−2.386	1.00	68.75	O
ATOM	558	CB	LEU	A	74	17.129	76.387	−1.422	1.00	79.09	C
ATOM	559	CG	LEU	A	74	18.119	75.337	−1.955	1.00	77.59	C
ATOM	560	CD1	LEU	A	74	18.173	75.258	−3.476	1.00	73.46	C
ATOM	561	CD2	LEU	A	74	19.496	75.607	−1.389	1.00	75.07	C
ATOM	562	N	CYS	A	75	14.979	74.522	−0.171	1.00	67.63	N
ATOM	563	CA	CYS	A	75	14.421	73.231	0.175	1.00	73.22	C
ATOM	564	C	CYS	A	75	13.039	73.036	−0.444	1.00	79.42	C
ATOM	565	O	CYS	A	75	12.753	71.960	−0.992	1.00	81.19	O
ATOM	566	CB	CYS	A	75	14.398	73.040	1.679	1.00	81.22	C
ATOM	567	SG	CYS	A	75	16.069	73.066	2.354	1.00	84.64	S
ATOM	568	N	ASP	A	76	12.206	74.083	−0.393	1.00	81.32	N
ATOM	569	CA	ASP	A	76	10.854	74.018	−0.939	1.00	80.83	C
ATOM	570	C	ASP	A	76	10.874	73.775	−2.431	1.00	77.44	C
ATOM	571	O	ASP	A	76	10.290	72.807	−2.903	1.00	74.40	O
ATOM	572	CB	ASP	A	76	10.040	75.259	−0.595	1.00	91.09	C
ATOM	573	CG	ASP	A	76	9.526	75.231	0.834	1.00	109.26	C
ATOM	574	OD1	ASP	A	76	8.977	76.263	1.283	1.00	117.74	O
ATOM	575	OD2	ASP	A	76	9.677	74.182	1.511	1.00	105.38	O
ATOM	576	N	LYS	A	77	11.570	74.622	−3.178	1.00	73.07	N
ATOM	577	CA	LYS	A	77	11.653	74.410	−4.617	1.00	80.26	C
ATOM	578	C	LYS	A	77	12.043	72.954	−4.896	1.00	83.81	C
ATOM	579	O	LYS	A	77	11.456	72.302	−5.770	1.00	93.85	O
ATOM	580	CB	LYS	A	77	12.638	75.387	−5.285	1.00	85.13	C
ATOM	581	CG	LYS	A	77	12.151	76.823	−5.497	1.00	95.80	C
ATOM	582	CD	LYS	A	77	11.189	77.006	−6.683	1.00	112.15	C
ATOM	583	CE	LYS	A	77	11.644	76.325	−7.980	1.00	122.30	C
ATOM	584	NZ	LYS	A	77	12.991	76.732	−8.493	1.00	125.25	N
ATOM	585	N	TYR	A	78	13.009	72.444	−4.130	1.00	78.20	N
ATOM	586	CA	TYR	A	78	13.538	71.108	−4.357	1.00	73.91	C
ATOM	587	C	TYR	A	78	12.469	70.059	−4.066	1.00	72.35	C
ATOM	588	O	TYR	A	78	12.107	69.284	−4.957	1.00	72.08	O
ATOM	589	CB	TYR	A	78	14.855	70.856	−3.574	1.00	71.42	C
ATOM	590	CG	TYR	A	78	15.203	69.386	−3.422	1.00	64.51	C
ATOM	591	CD1	TYR	A	78	15.735	68.650	−4.488	1.00	61.06	C
ATOM	592	CD2	TYR	A	78	14.944	68.722	−2.227	1.00	62.74	C
ATOM	593	CE1	TYR	A	78	16.022	67.295	−4.351	1.00	61.22	C
ATOM	594	CE2	TYR	A	78	15.216	67.370	−2.078	1.00	65.51	C
ATOM	595	CZ	TYR	A	78	15.756	66.659	−3.136	1.00	64.77	C
ATOM	596	OH	TYR	A	78	16.015	65.314	−2.961	1.00	69.46	O
ATOM	597	N	ASN	A	79	11.955	70.038	−2.838	1.00	68.62	N
ATOM	598	CA	ASN	A	79	10.869	69.106	−2.500	1.00	72.65	C
ATOM	599	C	ASN	A	79	9.685	69.110	−3.494	1.00	72.06	C
ATOM	600	O	ASN	A	79	9.203	68.061	−3.916	1.00	70.17	O
ATOM	601	CB	ASN	A	79	10.385	69.372	−1.097	1.00	67.49	C
ATOM	602	CG	ASN	A	79	11.470	69.156	−0.068	1.00	69.57	C
ATOM	603	OD1	ASN	A	79	11.925	68.037	0.129	1.00	78.52	O
ATOM	604	ND2	ASN	A	79	11.890	70.228	0.597	1.00	66.73	N
ATOM	605	N	ARG	A	80	9.259	70.300	−3.889	1.00	71.81	N
ATOM	606	CA	ARG	A	80	8.184	70.470	−4.844	1.00	68.65	C
ATOM	607	C	ARG	A	80	8.555	69.854	−6.178	1.00	72.24	C
ATOM	608	O	ARG	A	80	7.762	69.099	−6.771	1.00	78.48	O
ATOM	609	CB	ARG	A	80	7.809	71.958	−4.980	1.00	70.70	C
ATOM	610	CG	ARG	A	80	7.205	72.530	−3.695	1.00	74.40	C
ATOM	611	CD	ARG	A	80	6.360	73.762	−3.938	1.00	83.67	C
ATOM	612	NE	ARG	A	80	7.166	74.965	−4.111	1.00	94.25	N
ATOM	613	CZ	ARG	A	80	7.355	75.885	−3.165	1.00	100.87	C
ATOM	614	NH1	ARG	A	80	8.124	76.938	−3.422	1.00	97.57	N
ATOM	615	NH2	ARG	A	80	6.791	75.749	−1.963	1.00	97.00	N
ATOM	616	N	ALA	A	81	9.765	70.138	−6.653	1.00	74.35	N
ATOM	617	CA	ALA	A	81	10.206	69.521	−7.906	1.00	71.16	C
ATOM	618	C	ALA	A	81	10.272	67.998	−7.740	1.00	69.50	C
ATOM	619	O	ALA	A	81	9.994	67.242	−8.673	1.00	71.80	O
ATOM	620	CB	ALA	A	81	11.525	70.092	−8.364	1.00	64.33	C
ATOM	621	N	ILE	A	82	10.589	67.552	−6.532	1.00	70.22	N
ATOM	622	CA	ILE	A	82	10.635	66.125	−6.269	1.00	71.79	C
ATOM	623	C	ILE	A	82	9.265	65.539	−6.514	1.00	70.91	C
ATOM	624	O	ILE	A	82	9.125	64.621	−7.334	1.00	73.03	O
ATOM	625	CB	ILE	A	82	11.174	65.786	−4.856	1.00	68.20	C
ATOM	626	CG1	ILE	A	82	12.690	65.876	−4.852	1.00	62.07	C
ATOM	627	CG2	ILE	A	82	10.812	64.364	−4.453	1.00	65.62	C
ATOM	628	CD1	ILE	A	82	13.356	64.918	−5.832	1.00	58.52	C
ATOM	629	N	ASP	A	83	8.268	66.103	−5.825	1.00	71.85	N
ATOM	630	CA	ASP	A	83	6.856	65.737	−6.001	1.00	66.02	C
ATOM	631	C	ASP	A	83	6.544	65.715	−7.490	1.00	64.23	C
ATOM	632	O	ASP	A	83	6.109	64.700	−8.043	1.00	63.57	O
ATOM	633	CB	ASP	A	83	5.954	66.720	−5.250	1.00	58.99	C
ATOM	634	CG	ASP	A	83	6.044	66.550	−3.736	1.00	68.14	C
ATOM	635	OD1	ASP	A	83	6.458	65.470	−3.244	1.00	73.63	O
ATOM	636	OD2	ASP	A	83	5.720	67.508	−3.020	1.00	75.85	O
ATOM	637	N	SER	A	84	6.850	66.816	−8.157	1.00	58.55	N
ATOM	638	CA	SER	A	84	6.669	66.858	−9.582	1.00	64.08	C
ATOM	639	C	SER	A	84	7.259	65.628	−10.288	1.00	70.74	C
ATOM	640	O	SER	A	84	6.646	65.062	−11.185	1.00	81.23	O
ATOM	641	CB	SER	A	84	7.289	68.126	−10.119	1.00	66.16	C
ATOM	642	OG	SER	A	84	7.439	68.000	−11.507	1.00	79.82	O
ATOM	643	N	ILE	A	85	8.454	65.218	−9.883	1.00	76.70	N
ATOM	644	CA	ILE	A	85	9.145	64.136	−10.565	1.00	74.98	C
ATOM	645	C	ILE	A	85	8.425	62.825	−10.313	1.00	73.24	C
ATOM	646	O	ILE	A	85	8.180	62.056	−11.250	1.00	71.23	O
ATOM	647	CB	ILE	A	85	10.648	64.084	−10.162	1.00	76.94	C
ATOM	648	CG1	ILE	A	85	11.460	65.063	−11.019	1.00	74.86	C
ATOM	649	CG2	ILE	A	85	11.238	62.682	−10.273	1.00	65.77	C
ATOM	650	CD1	ILE	A	85	11.078	65.049	−12.485	1.00	78.80	C
ATOM	651	N	HIS	A	86	8.080	62.583	−9.050	1.00	66.21	N
ATOM	652	CA	HIS	A	86	7.372	61.370	−8.691	1.00	76.04	C
ATOM	653	C	HIS	A	86	6.097	61.253	−9.474	1.00	85.86	C
ATOM	654	O	HIS	A	86	5.690	60.155	−9.869	1.00	81.85	O
ATOM	655	CB	HIS	A	86	7.087	61.358	−7.212	1.00	77.32	C
ATOM	656	CG	HIS	A	86	8.307	61.108	−6.379	1.00	83.60	C
ATOM	657	ND1	HIS	A	86	8.518	61.719	−5.202	1.00	91.14	N
ATOM	658	CD2	HIS	A	86	9.414	60.288	−6.605	1.00	77.82	C
ATOM	659	CE1	HIS	A	86	9.691	61.294	−4.688	1.00	87.09	C
ATOM	660	NE2	HIS	A	86	10.238	60.428	−5.556	1.00	76.45	N
ATOM	661	N	GLN	A	87	5.472	62.400	−9.729	1.00	83.88	N
ATOM	662	CA	GLN	A	87	4.310	62.438	−10.576	1.00	81.50	C
ATOM	663	C	GLN	A	87	4.655	61.913	−11.959	1.00	82.93	C
ATOM	664	O	GLN	A	87	4.139	60.882	−12.360	1.00	94.72	O
ATOM	665	CB	GLN	A	87	3.647	63.822	−10.587	1.00	79.79	C
ATOM	666	CG	GLN	A	87	2.651	64.035	−9.436	1.00	78.40	C
ATOM	667	CD	GLN	A	87	1.540	62.976	−9.367	1.00	81.75	C
ATOM	668	OE1	GLN	A	87	0.930	62.616	−10.380	1.00	93.67	O
ATOM	669	NE2	GLN	A	87	1.275	62.478	−8.170	1.00	76.50	N
ATOM	670	N	LEU	A	88	5.565	62.577	−12.656	1.00	89.54	N
ATOM	671	CA	LEU	A	88	6.074	62.083	−13.945	1.00	89.27	C
ATOM	672	C	LEU	A	88	6.244	60.551	−14.046	1.00	90.72	C
ATOM	673	O	LEU	A	88	5.975	59.954	−15.092	1.00	92.50	O
ATOM	674	CB	LEU	A	88	7.393	62.776	−14.267	1.00	84.31	C
ATOM	675	CG	LEU	A	88	7.868	62.785	−15.713	1.00	87.02	C
ATOM	676	CD1	LEU	A	88	6.736	63.161	−16.652	1.00	99.55	C
ATOM	677	CD2	LEU	A	88	9.008	63.774	−15.862	1.00	92.23	C
ATOM	678	N	TRP	A	89	6.662	59.914	−12.958	1.00	86.97	N
ATOM	679	CA	TRP	A	89	6.906	58.475	−12.988	1.00	95.62	C
ATOM	680	C	TRP	A	89	5.672	57.628	−12.900	1.00	101.61	C
ATOM	681	O	TRP	A	89	5.744	56.399	−13.015	1.00	114.72	O
ATOM	682	CB	TRP	A	89	7.856	58.062	−11.877	1.00	98.45	C
ATOM	683	CG	TRP	A	89	9.232	58.672	−11.949	1.00	96.77	C
ATOM	684	CD1	TRP	A	89	9.818	59.373	−13.009	1.00	93.23	C
ATOM	685	CD2	TRP	A	89	10.268	58.608	−10.913	1.00	100.86	C
ATOM	686	NE1	TRP	A	89	11.097	59.752	−12.695	1.00	87.91	N
ATOM	687	CE2	TRP	A	89	11.432	59.324	−11.453	1.00	93.56	C
ATOM	688	CE3	TRP	A	89	10.341	58.058	−9.623	1.00	100.33	C
ATOM	689	CZ2	TRP	A	89	12.602	59.470	−10.719	1.00	89.47	C
ATOM	690	CZ3	TRP	A	89	11.523	58.219	−8.892	1.00	88.13	C
ATOM	691	CH2	TRP	A	89	12.625	58.907	−9.428	1.00	90.79	C
ATOM	692	N	LYS	A	90	4.531	58.257	−12.653	1.00	102.93	N
ATOM	693	CA	LYS	A	90	3.257	57.545	−12.680	1.00	92.58	C
ATOM	694	C	LYS	A	90	2.765	57.516	−14.123	1.00	97.63	C
ATOM	695	O	LYS	A	90	2.170	56.524	−14.553	1.00	101.37	O
ATOM	696	CB	LYS	A	90	2.247	58.212	−11.757	1.00	82.86	C
ATOM	697	CG	LYS	A	90	2.564	58.055	−10.277	1.00	77.63	C
ATOM	698	CD	LYS	A	90	1.956	59.193	−9.463	1.00	80.30	C
ATOM	699	CE	LYS	A	90	2.123	58.963	−7.968	1.00	75.80	C
ATOM	700	NZ	LYS	A	90	1.466	57.693	−7.578	1.00	82.12	N
ATOM	701	N	GLY	A	91	3.045	58.600	−14.860	1.00	88.91	N
ATOM	702	CA	GLY	A	91	2.852	58.664	−16.308	1.00	89.54	C
ATOM	703	C	GLY	A	91	3.721	57.632	−16.992	1.00	100.34	C
ATOM	704	O	GLY	A	91	4.349	56.808	−16.320	1.00	106.30	O
ATOM	705	N	THR	A	92	3.774	57.657	−18.322	1.00	113.56	N
ATOM	706	CA	THR	A	92	4.501	56.596	−19.047	1.00	124.37	C
ATOM	707	C	THR	A	92	6.024	56.667	−18.911	1.00	127.99	C
ATOM	708	O	THR	A	92	6.713	55.689	−19.209	1.00	139.09	O
ATOM	709	CB	THR	A	92	4.083	56.440	−20.531	1.00	123.30	C
ATOM	710	OG1	THR	A	92	3.526	57.670	−21.018	1.00	124.09	O
ATOM	711	CG2	THR	A	92	3.057	55.308	−20.677	1.00	111.43	C
ATOM	712	N	THR	A	93	6.537	57.808	−18.446	1.00	124.74	N
ATOM	713	CA	THR	A	93	7.959	57.937	−18.133	1.00	128.33	C
ATOM	714	C	THR	A	93	8.296	56.920	−17.054	1.00	131.44	C
ATOM	715	O	THR	A	93	7.515	56.726	−16.116	1.00	132.48	O
ATOM	716	CB	THR	A	93	8.320	59.349	−17.628	1.00	130.21	C
ATOM	717	OG1	THR	A	93	7.540	60.328	−18.330	1.00	131.88	O
ATOM	718	CG2	THR	A	93	9.822	59.638	−17.817	1.00	118.25	C
ATOM	719	N	GLN	A	94	9.442	56.261	−17.207	1.00	131.90	N
ATOM	720	CA	GLN	A	94	9.902	55.252	−16.250	1.00	130.17	C
ATOM	721	C	GLN	A	94	10.865	55.832	−15.208	1.00	127.33	C
ATOM	722	O	GLN	A	94	11.574	56.815	−15.485	1.00	107.01	O
ATOM	723	CB	GLN	A	94	10.541	54.049	−16.961	1.00	131.32	C
ATOM	724	CG	GLN	A	94	11.704	54.392	−17.877	1.00	143.44	C
ATOM	725	CD	GLN	A	94	11.241	54.931	−19.218	1.00	153.35	C
ATOM	726	OE1	GLN	A	94	10.764	54.178	−20.069	1.00	161.04	O
ATOM	727	NE2	GLN	A	94	11.375	56.241	−19.411	1.00	152.41	N
ATOM	728	N	PRO	A	95	10.879	55.231	−13.997	1.00	130.11	N
ATOM	729	CA	PRO	A	95	11.812	55.644	−12.956	1.00	133.38	C
ATOM	730	C	PRO	A	95	13.255	55.673	−13.443	1.00	143.04	C
ATOM	731	O	PRO	A	95	13.642	54.890	−14.318	1.00	152.16	O
ATOM	732	CB	PRO	A	95	11.657	54.554	−11.891	1.00	126.80	C
ATOM	733	CG	PRO	A	95	10.261	54.074	−12.047	1.00	123.46	C
ATOM	734	CD	PRO	A	95	9.936	54.202	−13.510	1.00	128.38	C
ATOM	735	N	MET	A	96	14.020	56.610	−12.888	1.00	146.82	N
ATOM	736	CA	MET	A	96	15.473	56.593	−12.918	1.00	138.87	C
ATOM	737	C	MET	A	96	15.925	55.157	−12.638	1.00	146.28	C
ATOM	738	O	MET	A	96	15.455	54.521	−11.675	1.00	131.23	O
ATOM	739	CB	MET	A	96	15.998	57.565	−11.847	1.00	130.22	C
ATOM	740	CG	MET	A	96	17.433	57.363	−11.367	1.00	130.45	C
ATOM	741	SD	MET	A	96	17.625	57.551	−9.571	1.00	107.47	S
ATOM	742	CE	MET	A	96	17.762	55.848	−9.035	1.00	109.11	C
ATOM	743	N	LYS	A	97	16.804	54.645	−13.504	1.00	145.31	N
ATOM	744	CA	LYS	A	97	17.333	53.291	−13.378	1.00	136.45	C
ATOM	745	C	LYS	A	97	17.568	52.970	−11.904	1.00	133.95	C
ATOM	746	O	LYS	A	97	18.369	53.629	−11.236	1.00	131.48	O
ATOM	747	CB	LYS	A	97	18.607	53.141	−14.208	1.00	140.73	C
ATOM	748	CG	LYS	A	97	18.341	52.858	−15.685	1.00	144.90	C
ATOM	749	CD	LYS	A	97	19.612	52.823	−16.536	1.00	146.26	C
ATOM	750	CE	LYS	A	97	20.734	51.987	−15.924	1.00	141.73	C
ATOM	751	NZ	LYS	A	97	20.263	50.692	−15.351	1.00	135.31	N
ATOM	752	N	LEU	A	98	16.838	51.969	−11.413	1.00	126.94	N
ATOM	753	CA	LEU	A	98	16.679	51.708	−9.978	1.00	129.38	C
ATOM	754	C	LEU	A	98	18.004	51.671	−9.202	1.00	128.73	C
ATOM	755	O	LEU	A	98	18.471	52.703	−8.708	1.00	129.72	O
ATOM	756	CB	LEU	A	98	15.873	50.413	−9.761	1.00	132.47	C
ATOM	757	CG	LEU	A	98	14.673	50.377	−8.796	1.00	135.04	C
ATOM	758	CD1	LEU	A	98	14.042	48.986	−8.793	1.00	130.64	C
ATOM	759	CD2	LEU	A	98	15.015	50.821	−7.374	1.00	122.78	C
ATOM	760	N	ASN	A	99	18.610	50.491	−9.104	1.00	124.55	N
ATOM	761	CA	ASN	A	99	19.844	50.337	−8.337	1.00	117.94	C
ATOM	762	C	ASN	A	99	21.152	50.249	−9.149	1.00	111.55	C
ATOM	763	O	ASN	A	99	21.624	49.176	−9.532	1.00	107.36	O
ATOM	764	CB	ASN	A	99	19.705	49.214	−7.304	1.00	120.86	C
ATOM	765	CG	ASN	A	99	19.319	49.739	−5.930	1.00	130.51	C
ATOM	766	OD1	ASN	A	99	18.676	50.787	−5.807	1.00	128.58	O
ATOM	767	ND2	ASN	A	99	19.722	49.018	−4.884	1.00	126.01	N
ATOM	768	N	THR	A	100	21.716	51.422	−9.401	1.00	99.27	N
ATOM	769	CA	THR	A	100	23.004	51.559	−10.036	1.00	84.48	C
ATOM	770	C	THR	A	100	24.037	51.916	−8.955	1.00	81.45	C
ATOM	771	O	THR	A	100	23.679	52.129	−7.796	1.00	79.69	O
ATOM	772	CB	THR	A	100	22.954	52.678	−11.082	1.00	90.64	C
ATOM	773	OG1	THR	A	100	22.728	53.928	−10.421	1.00	101.48	O
ATOM	774	CG2	THR	A	100	21.839	52.436	−12.089	1.00	84.67	C
ATOM	775	N	ARG	A	101	25.318	51.950	−9.322	1.00	82.50	N
ATOM	776	CA	ARG	A	101	26.379	52.358	−8.395	1.00	78.88	C
ATOM	777	C	ARG	A	101	26.455	53.869	−8.460	1.00	67.03	C
ATOM	778	O	ARG	A	101	26.168	54.454	−9.501	1.00	67.48	O
ATOM	779	CB	ARG	A	101	27.754	51.801	−8.792	1.00	83.50	C
ATOM	780	CG	ARG	A	101	27.851	50.305	−8.959	1.00	87.94	C
ATOM	781	CD	ARG	A	101	27.958	49.620	−7.622	1.00	94.96	C
ATOM	782	NE	ARG	A	101	27.838	48.176	−7.769	1.00	108.04	N
ATOM	783	CZ	ARG	A	101	28.076	47.312	−6.794	1.00	113.43	C
ATOM	784	NH1	ARG	A	101	27.938	46.013	−7.017	1.00	125.92	N
ATOM	785	NH2	ARG	A	101	28.466	47.749	−5.603	1.00	113.65	N
ATOM	786	N	PRO	A	102	26.845	54.508	−7.356	1.00	56.93	N
ATOM	787	CA	PRO	A	102	26.973	55.947	−7.436	1.00	55.76	C
ATOM	788	C	PRO	A	102	28.191	56.280	−8.251	1.00	60.15	C
ATOM	789	O	PRO	A	102	29.167	55.557	−8.196	1.00	65.44	O
ATOM	790	CB	PRO	A	102	27.192	56.378	−5.989	1.00	56.65	C
ATOM	791	CG	PRO	A	102	27.561	55.139	−5.244	1.00	61.03	C
ATOM	792	CD	PRO	A	102	26.950	53.992	−5.982	1.00	57.05	C
ATOM	793	N	SER	A	103	28.133	57.367	−9.008	1.00	61.82	N
ATOM	794	CA	SER	A	103	29.306	57.896	−9.663	1.00	55.75	C
ATOM	795	C	SER	A	103	30.319	58.282	−8.586	1.00	60.21	C
ATOM	796	O	SER	A	103	30.010	58.267	−7.385	1.00	61.78	O
ATOM	797	CB	SER	A	103	28.900	59.129	−10.456	1.00	57.20	C
ATOM	798	OG	SER	A	103	28.527	60.166	−9.565	1.00	62.31	O
ATOM	799	N	THR	A	104	31.524	58.653	−9.000	1.00	63.33	N
ATOM	800	CA	THR	A	104	32.560	58.948	−8.028	1.00	60.38	C
ATOM	801	C	THR	A	104	32.188	60.184	−7.299	1.00	61.55	C
ATOM	802	O	THR	A	104	32.177	60.201	−6.060	1.00	66.82	O
ATOM	803	CB	THR	A	104	33.937	59.102	−8.680	1.00	62.90	C
ATOM	804	OG1	THR	A	104	34.346	57.809	−9.136	1.00	63.80	O
ATOM	805	CG2	THR	A	104	34.973	59.638	−7.676	1.00	56.51	C
ATOM	806	N	GLY	A	105	31.858	61.216	−8.067	1.00	64.25	N
ATOM	807	CA	GLY	A	105	31.432	62.494	−7.477	1.00	67.54	C
ATOM	808	C	GLY	A	105	30.351	62.335	−6.419	1.00	69.90	C
ATOM	809	O	GLY	A	105	30.435	62.913	−5.328	1.00	73.44	O
ATOM	810	N	LEU	A	106	29.332	61.540	−6.725	1.00	63.26	N
ATOM	811	CA	LEU	A	106	28.288	61.378	−5.763	1.00	63.45	C
ATOM	812	C	LEU	A	106	28.840	60.679	−4.538	1.00	64.15	C
ATOM	813	O	LEU	A	106	28.576	61.089	−3.404	1.00	66.48	O
ATOM	814	CB	LEU	A	106	27.105	60.615	−6.358	1.00	65.67	C
ATOM	815	CG	LEU	A	106	26.004	60.209	−5.367	1.00	62.67	C
ATOM	816	CD1	LEU	A	106	25.490	61.389	−4.571	1.00	68.09	C
ATOM	817	CD2	LEU	A	106	24.871	59.564	−6.130	1.00	65.84	C
ATOM	818	N	LEU	A	107	29.601	59.617	−4.780	1.00	63.18	N
ATOM	819	CA	LEU	A	107	30.163	58.810	−3.709	1.00	59.25	C
ATOM	820	C	LEU	A	107	31.000	59.642	−2.740	1.00	56.53	C
ATOM	821	O	LEU	A	107	30.907	59.461	−1.516	1.00	53.84	O
ATOM	822	CB	LEU	A	107	31.021	57.701	−4.295	1.00	62.81	C
ATOM	823	CG	LEU	A	107	31.523	56.654	−3.307	1.00	60.96	C
ATOM	824	CD1	LEU	A	107	30.447	56.370	−2.264	1.00	58.12	C
ATOM	825	CD2	LEU	A	107	31.908	55.401	−4.079	1.00	50.17	C
ATOM	826	N	ARG	A	108	31.807	60.552	−3.279	1.00	48.39	N
ATOM	827	CA	ARG	A	108	32.637	61.376	−2.422	1.00	51.93	C
ATOM	828	C	ARG	A	108	31.704	62.171	−1.529	1.00	54.56	C
ATOM	829	O	ARG	A	108	31.895	62.240	−0.313	1.00	57.93	O
ATOM	830	CB	ARG	A	108	33.555	62.290	−3.238	1.00	55.00	C
ATOM	831	CG	ARG	A	108	34.570	63.044	−2.398	1.00	64.84	C
ATOM	832	CD	ARG	A	108	35.135	64.295	−3.069	1.00	71.28	C
ATOM	833	NE	ARG	A	108	36.017	63.983	−4.190	1.00	85.87	N
ATOM	834	CZ	ARG	A	108	35.622	63.854	−5.459	1.00	98.66	C
ATOM	835	NH1	ARG	A	108	34.346	64.015	−5.797	1.00	112.24	N
ATOM	836	NH2	ARG	A	108	36.506	63.559	−6.405	1.00	103.90	N
ATOM	837	N	HIS	A	109	30.652	62.730	−2.128	1.00	61.45	N
ATOM	838	CA	HIS	A	109	29.640	63.464	−1.357	1.00	56.46	C
ATOM	839	C	HIS	A	109	29.029	62.608	−0.303	1.00	57.01	C
ATOM	840	O	HIS	A	109	29.123	62.934	0.890	1.00	56.24	O
ATOM	841	CB	HIS	A	109	28.556	64.044	−2.243	1.00	61.80	C
ATOM	842	CG	HIS	A	109	27.449	64.691	−1.466	1.00	67.05	C
ATOM	843	ND1	HIS	A	109	27.594	65.885	−0.865	1.00	67.02	N
ATOM	844	CD2	HIS	A	109	26.166	64.243	−1.161	1.00	62.56	C
ATOM	845	CE1	HIS	A	109	26.464	66.185	−0.212	1.00	63.34	C
ATOM	846	NE2	HIS	A	109	25.593	65.174	−0.394	1.00	63.52	N
ATOM	847	N	ILE	A	110	28.427	61.487	−0.712	1.00	53.30	N
ATOM	848	CA	ILE	A	110	27.773	60.609	0.253	1.00	53.14	C
ATOM	849	C	ILE	A	110	28.687	60.290	1.424	1.00	57.87	C
ATOM	850	O	ILE	A	110	28.265	60.311	2.577	1.00	57.73	O
ATOM	851	CB	ILE	A	110	27.400	59.275	−0.362	1.00	53.96	C
ATOM	852	CG1	ILE	A	110	26.405	59.466	−1.507	1.00	59.80	C
ATOM	853	CG2	ILE	A	110	26.884	58.361	0.732	1.00	50.95	C
ATOM	854	CD1	ILE	A	110	25.724	58.186	−1.920	1.00	58.03	C
ATOM	855	N	LEU	A	111	29.946	59.973	1.127	1.00	60.59	N
ATOM	856	CA	LEU	A	111	30.845	59.535	2.181	1.00	62.61	C
ATOM	857	C	LEU	A	111	31.183	60.688	3.115	1.00	63.24	C
ATOM	858	O	LEU	A	111	31.341	60.497	4.324	1.00	63.63	O
ATOM	859	CB	LEU	A	111	32.099	58.885	1.606	1.00	65.04	C
ATOM	860	CG	LEU	A	111	31.953	57.466	1.037	1.00	65.15	C
ATOM	861	CD1	LEU	A	111	33.184	57.087	0.225	1.00	58.67	C
ATOM	862	CD2	LEU	A	111	31.713	56.452	2.142	1.00	63.50	C
ATOM	863	N	GLN	A	112	31.266	61.892	2.556	1.00	60.51	N
ATOM	864	CA	GLN	A	112	31.465	63.074	3.369	1.00	58.56	C
ATOM	865	C	GLN	A	112	30.292	63.183	4.351	1.00	62.16	C
ATOM	866	O	GLN	A	112	30.473	63.430	5.542	1.00	63.02	O
ATOM	867	CB	GLN	A	112	31.562	64.279	2.460	1.00	57.15	C
ATOM	868	CG	GLN	A	112	31.897	65.580	3.153	1.00	68.74	C
ATOM	869	CD	GLN	A	112	33.194	65.517	3.930	1.00	76.93	C
ATOM	870	OE1	GLN	A	112	33.209	65.696	5.150	1.00	83.36	O
ATOM	871	NE2	GLN	A	112	34.295	65.269	3.227	1.00	80.34	N
ATOM	872	N	GLN	A	113	29.093	62.920	3.840	1.00	61.95	N
ATOM	873	CA	GLN	A	113	27.845	63.093	4.569	1.00	58.69	C
ATOM	874	C	GLN	A	113	27.820	62.091	5.703	1.00	63.45	C
ATOM	875	O	GLN	A	113	27.680	62.457	6.872	1.00	67.22	O
ATOM	876	CB	GLN	A	113	26.729	62.822	3.585	1.00	60.48	C
ATOM	877	CG	GLN	A	113	25.409	63.484	3.826	1.00	63.50	C
ATOM	878	CD	GLN	A	113	24.564	63.488	2.567	1.00	68.85	C
ATOM	879	OE1	GLN	A	113	24.746	62.664	1.674	1.00	64.48	O
ATOM	880	NE2	GLN	A	113	23.647	64.436	2.480	1.00	75.50	N
ATOM	881	N	VAL	A	114	28.007	60.822	5.343	1.00	66.90	N
ATOM	882	CA	VAL	A	114	28.072	59.715	6.298	1.00	65.23	C
ATOM	883	C	VAL	A	114	29.078	59.996	7.430	1.00	64.65	C
ATOM	884	O	VAL	A	114	28.779	59.829	8.624	1.00	52.29	O
ATOM	885	CB	VAL	A	114	28.430	58.415	5.558	1.00	65.61	C
ATOM	886	CG1	VAL	A	114	28.723	57.279	6.535	1.00	63.46	C
ATOM	887	CG2	VAL	A	114	27.306	58.047	4.598	1.00	67.38	C
ATOM	888	N	TYR	A	115	30.267	60.445	7.041	1.00	62.83	N
ATOM	889	CA	TYR	A	115	31.294	60.750	7.998	1.00	65.62	C
ATOM	890	C	TYR	A	115	30.821	61.801	9.012	1.00	69.83	C
ATOM	891	O	TYR	A	115	30.814	61.562	10.228	1.00	64.49	O
ATOM	892	CB	TYR	A	115	32.531	61.227	7.272	1.00	67.22	C
ATOM	893	CG	TYR	A	115	33.677	61.417	8.206	1.00	76.50	C
ATOM	894	CD1	TYR	A	115	34.412	60.319	8.668	1.00	80.03	C
ATOM	895	CD2	TYR	A	115	34.022	62.685	8.649	1.00	73.27	C
ATOM	896	CE1	TYR	A	115	35.469	60.487	9.538	1.00	81.41	C
ATOM	897	CE2	TYR	A	115	35.070	62.864	9.524	1.00	85.68	C
ATOM	898	CZ	TYR	A	115	35.788	61.763	9.968	1.00	86.44	C
ATOM	899	OH	TYR	A	115	36.834	61.961	10.835	1.00	88.49	O
ATOM	900	N	ASN	A	116	30.401	62.952	8.494	1.00	71.64	N
ATOM	901	CA	ASN	A	116	29.921	64.056	9.318	1.00	72.44	C
ATOM	902	C	ASN	A	116	28.750	63.704	10.220	1.00	72.82	C
ATOM	903	O	ASN	A	116	28.647	64.221	11.312	1.00	74.59	O
ATOM	904	CB	ASN	A	116	29.545	65.235	8.437	1.00	74.94	C
ATOM	905	CG	ASN	A	116	30.749	65.877	7.800	1.00	73.10	C
ATOM	906	OD1	ASN	A	116	30.728	66.216	6.625	1.00	79.46	O
ATOM	907	ND2	ASN	A	116	31.810	66.043	8.573	1.00	66.31	N
ATOM	908	N	HIS	A	117	27.873	62.823	9.765	1.00	70.88	N
ATOM	909	CA	HIS	A	117	26.789	62.366	10.611	1.00	74.29	C
ATOM	910	C	HIS	A	117	27.198	61.300	11.588	1.00	80.60	C
ATOM	911	O	HIS	A	117	26.472	61.021	12.537	1.00	89.20	O
ATOM	912	CB	HIS	A	117	25.622	61.897	9.759	1.00	73.06	C
ATOM	913	CG	HIS	A	117	24.824	63.032	9.166	1.00	80.50	C
ATOM	914	ND1	HIS	A	117	23.832	63.652	9.840	1.00	75.00	N
ATOM	915	CD2	HIS	A	117	24.922	63.674	7.929	1.00	78.39	C
ATOM	916	CE1	HIS	A	117	23.312	64.619	9.065	1.00	77.93	C
ATOM	917	NE2	HIS	A	117	23.984	64.633	7.898	1.00	70.97	N
ATOM	918	N	SER	A	118	28.355	60.680	11.374	1.00	85.56	N
ATOM	919	CA	SER	A	118	28.756	59.548	12.208	1.00	80.05	C
ATOM	920	C	SER	A	118	29.826	59.946	13.203	1.00	83.59	C
ATOM	921	O	SER	A	118	29.801	59.489	14.343	1.00	83.66	O
ATOM	922	CB	SER	A	118	29.256	58.385	11.354	1.00	79.81	C
ATOM	923	OG	SER	A	118	28.256	57.915	10.468	1.00	76.84	O
ATOM	924	N	VAL	A	119	30.754	60.802	12.773	1.00	79.90	N
ATOM	925	CA	VAL	A	119	31.882	61.166	13.604	1.00	87.15	C
ATOM	926	C	VAL	A	119	31.578	62.449	14.349	1.00	100.88	C
ATOM	927	O	VAL	A	119	32.121	63.515	14.043	1.00	95.38	O
ATOM	928	CB	VAL	A	119	33.188	61.247	12.803	1.00	93.33	C
ATOM	929	CG1	VAL	A	119	34.377	61.464	13.731	1.00	94.98	C
ATOM	930	CG2	VAL	A	119	33.379	59.957	12.031	1.00	94.99	C
ATOM	931	N	THR	A	120	30.686	62.296	15.332	1.00	119.28	N
ATOM	932	CA	THR	A	120	30.202	63.340	16.244	1.00	118.20	C
ATOM	933	C	THR	A	120	31.315	64.241	16.766	1.00	112.85	C
ATOM	934	O	THR	A	120	31.226	65.458	16.692	1.00	112.70	O
ATOM	935	CB	THR	A	120	29.488	62.694	17.455	1.00	127.11	C
ATOM	936	OG1	THR	A	120	30.346	61.698	18.043	1.00	118.89	O
ATOM	937	CG2	THR	A	120	28.165	62.032	17.028	1.00	124.57	C
ATOM	938	N	ASP	A	121	32.373	63.631	17.278	1.00	117.23	N
ATOM	939	CA	ASP	A	121	33.465	64.378	17.864	1.00	123.50	C
ATOM	940	C	ASP	A	121	34.766	63.929	17.215	1.00	119.87	C
ATOM	941	O	ASP	A	121	35.386	62.976	17.688	1.00	122.34	O
ATOM	942	CB	ASP	A	121	33.497	64.114	19.369	1.00	134.09	C
ATOM	943	CG	ASP	A	121	34.190	65.214	20.148	1.00	136.35	C
ATOM	944	OD1	ASP	A	121	35.336	65.576	19.805	1.00	122.11	O
ATOM	945	OD2	ASP	A	121	33.580	65.708	21.119	1.00	141.06	O
ATOM	946	N	PRO	A	122	35.187	64.607	16.126	1.00	120.35	N
ATOM	947	CA	PRO	A	122	36.358	64.129	15.371	1.00	122.06	C
ATOM	948	C	PRO	A	122	37.653	64.168	16.186	1.00	127.08	C
ATOM	949	O	PRO	A	122	38.742	64.091	15.616	1.00	129.82	O
ATOM	950	CB	PRO	A	122	36.428	65.081	14.162	1.00	114.37	C
ATOM	951	CG	PRO	A	122	35.672	66.296	14.568	1.00	117.18	C
ATOM	952	CD	PRO	A	122	34.637	65.862	15.574	1.00	120.56	C
ATOM	953	N	GLU	A	123	37.518	64.246	17.510	1.00	136.72	N
ATOM	954	CA	GLU	A	123	38.648	64.473	18.412	1.00	143.18	C
ATOM	955	C	GLU	A	123	39.295	63.213	18.978	1.00	138.57	C
ATOM	956	O	GLU	A	123	40.519	63.164	19.111	1.00	144.46	O
ATOM	957	CB	GLU	A	123	38.251	65.419	19.550	1.00	152.95	C
ATOM	958	CG	GLU	A	123	39.204	66.590	19.717	1.00	153.07	C
ATOM	959	CD	GLU	A	123	39.515	67.245	18.386	1.00	156.95	C
ATOM	960	OE1	GLU	A	123	38.567	67.719	17.719	1.00	159.53	O
ATOM	961	OE2	GLU	A	123	40.703	67.266	17.998	1.00	153.41	O
ATOM	962	N	LYS	A	124	38.491	62.205	19.312	1.00	130.92	N
ATOM	963	CA	LYS	A	124	39.032	60.913	19.752	1.00	130.53	C
ATOM	964	C	LYS	A	124	39.794	60.173	18.635	1.00	125.97	C
ATOM	965	O	LYS	A	124	39.635	58.967	18.485	1.00	132.10	O
ATOM	966	CB	LYS	A	124	37.928	59.998	20.317	1.00	128.86	C
ATOM	967	CG	LYS	A	124	37.458	60.310	21.732	1.00	132.67	C
ATOM	968	CD	LYS	A	124	35.995	60.750	21.793	1.00	136.53	C
ATOM	969	CE	LYS	A	124	35.765	62.148	21.224	1.00	136.94	C
ATOM	970	NZ	LYS	A	124	36.738	63.163	21.726	1.00	139.69	N
ATOM	971	N	LEU	A	125	40.617	60.885	17.861	1.00	119.99	N
ATOM	972	CA	LEU	A	125	41.421	60.255	16.802	1.00	126.90	C
ATOM	973	C	LEU	A	125	42.905	60.746	16.759	1.00	139.53	C
ATOM	974	O	LEU	A	125	43.443	61.066	15.684	1.00	132.34	O
ATOM	975	CB	LEU	A	125	40.708	60.366	15.430	1.00	128.46	C
ATOM	976	CG	LEU	A	125	39.223	59.950	15.210	1.00	130.27	C
ATOM	977	CD1	LEU	A	125	38.751	60.304	13.803	1.00	117.63	C
ATOM	978	CD2	LEU	A	125	38.903	58.479	15.484	1.00	112.25	C
ATOM	979	N	ASN	A	126	43.538	60.790	17.943	1.00	137.85	N
ATOM	980	CA	ASN	A	126	44.980	61.119	18.152	1.00	136.10	C
ATOM	981	C	ASN	A	126	45.439	62.527	17.751	1.00	139.55	C
ATOM	982	O	ASN	A	126	46.619	62.878	17.910	1.00	121.24	O
ATOM	983	CB	ASN	A	126	45.911	60.075	17.508	1.00	137.81	C
ATOM	984	CG	ASN	A	126	45.380	58.661	17.630	1.00	149.55	C
ATOM	985	OD1	ASN	A	126	45.518	57.857	16.707	1.00	157.87	O
ATOM	986	ND2	ASN	A	126	44.758	58.352	18.765	1.00	141.82	N
ATOM	987	N	SER	A	132	47.864	64.204	16.275	1.00	101.21	N
ATOM	988	CA	SER	A	132	48.410	65.118	15.262	1.00	122.44	C
ATOM	989	C	SER	A	132	48.519	64.512	13.863	1.00	139.57	C
ATOM	990	O	SER	A	132	48.132	65.172	12.897	1.00	132.12	O
ATOM	991	CB	SER	A	132	49.804	65.628	15.642	1.00	111.03	C
ATOM	992	OG	SER	A	132	50.249	65.054	16.852	1.00	102.89	O
ATOM	993	N	PRO	A	133	49.070	63.272	13.745	1.00	163.86	N
ATOM	994	CA	PRO	A	133	49.451	62.751	12.427	1.00	162.56	C
ATOM	995	C	PRO	A	133	48.349	61.950	11.726	1.00	165.94	C
ATOM	996	O	PRO	A	133	47.515	61.317	12.390	1.00	147.54	O
ATOM	997	CB	PRO	A	133	50.641	61.844	12.754	1.00	163.69	C
ATOM	998	CG	PRO	A	133	50.400	61.385	14.165	1.00	173.13	C
ATOM	999	CD	PRO	A	133	49.352	62.273	14.797	1.00	171.35	C
ATOM	1000	N	GLU	A	134	48.372	61.978	10.391	1.00	175.67	N
ATOM	1001	CA	GLU	A	134	47.368	61.298	9.562	1.00	176.01	C
ATOM	1002	C	GLU	A	134	47.433	59.775	9.657	1.00	181.24	C
ATOM	1003	O	GLU	A	134	47.803	59.085	8.702	1.00	178.60	O
ATOM	1004	CB	GLU	A	134	47.414	61.775	8.101	1.00	163.24	C
ATOM	1005	CG	GLU	A	134	46.285	62.735	7.764	1.00	153.63	C
ATOM	1006	CD	GLU	A	134	44.976	62.290	8.392	1.00	151.75	C
ATOM	1007	OE1	GLU	A	134	44.453	63.009	9.280	1.00	148.47	O
ATOM	1008	OE2	GLU	A	134	44.496	61.195	8.027	1.00	145.23	O
ATOM	1009	N	VAL	A	135	47.044	59.277	10.829	1.00	184.91	N
ATOM	1010	CA	VAL	A	135	47.088	57.855	11.157	1.00	171.52	C
ATOM	1011	C	VAL	A	135	45.728	57.188	10.911	1.00	160.47	C
ATOM	1012	O	VAL	A	135	45.456	56.106	11.425	1.00	151.48	O
ATOM	1013	CB	VAL	A	135	47.602	57.622	12.609	1.00	171.02	C
ATOM	1014	CG1	VAL	A	135	49.040	58.109	12.741	1.00	164.38	C
ATOM	1015	CG2	VAL	A	135	46.728	58.330	13.642	1.00	166.42	C
ATOM	1016	N	TYR	A	136	44.887	57.850	10.114	1.00	168.20	N
ATOM	1017	CA	TYR	A	136	43.557	57.346	9.744	1.00	167.70	C
ATOM	1018	C	TYR	A	136	43.227	57.592	8.268	1.00	171.31	C
ATOM	1019	O	TYR	A	136	42.400	56.881	7.694	1.00	162.08	O
ATOM	1020	CB	TYR	A	136	42.463	57.968	10.631	1.00	163.81	C
ATOM	1021	CG	TYR	A	136	42.534	57.536	12.079	1.00	156.53	C
ATOM	1022	CD1	TYR	A	136	41.942	56.341	12.501	1.00	147.41	C
ATOM	1023	CD2	TYR	A	136	43.201	58.315	13.025	1.00	155.46	C
ATOM	1024	CE1	TYR	A	136	42.013	55.933	13.826	1.00	142.26	C
ATOM	1025	CE2	TYR	A	136	43.278	57.917	14.353	1.00	158.31	C
ATOM	1026	CZ	TYR	A	136	42.684	56.727	14.748	1.00	152.05	C
ATOM	1027	OH	TYR	A	136	42.765	56.333	16.065	1.00	142.63	O
ATOM	1028	N	GLY	A	137	43.868	58.603	7.670	1.00	179.02	N
ATOM	1029	CA	GLY	A	137	43.643	58.983	6.267	1.00	172.75	C
ATOM	1030	C	GLY	A	137	42.285	59.626	6.030	1.00	175.73	C
ATOM	1031	O	GLY	A	137	41.326	58.934	5.666	1.00	182.03	O
ATOM	1032	N	GLU	A	138	42.202	60.950	6.217	1.00	168.72	N
ATOM	1033	CA	GLU	A	138	40.911	61.658	6.170	1.00	149.94	C
ATOM	1034	C	GLU	A	138	40.428	62.076	4.766	1.00	142.97	C
ATOM	1035	O	GLU	A	138	39.229	62.006	4.494	1.00	140.45	O
ATOM	1036	CB	GLU	A	138	40.881	62.843	7.154	1.00	146.92	C
ATOM	1037	CG	GLU	A	138	41.414	62.555	8.560	1.00	145.42	C
ATOM	1038	CD	GLU	A	138	40.710	61.415	9.301	1.00	151.96	C
ATOM	1039	OE1	GLU	A	138	40.850	61.341	10.544	1.00	150.62	O
ATOM	1040	OE2	GLU	A	138	40.029	60.578	8.667	1.00	145.79	O
ATOM	1041	N	THR	A	139	41.344	62.502	3.888	1.00	141.72	N
ATOM	1042	CA	THR	A	139	40.996	62.856	2.489	1.00	140.28	C
ATOM	1043	C	THR	A	139	41.620	61.926	1.429	1.00	133.27	C
ATOM	1044	O	THR	A	139	41.800	62.324	0.259	1.00	140.99	O
ATOM	1045	CB	THR	A	139	41.361	64.317	2.134	1.00	137.70	C
ATOM	1046	OG1	THR	A	139	41.200	65.152	3.288	1.00	130.49	O
ATOM	1047	CG2	THR	A	139	40.485	64.832	0.963	1.00	126.64	C
ATOM	1048	N	SER	A	140	41.927	60.689	1.826	1.00	95.09	N
ATOM	1049	CA	SER	A	140	42.460	59.723	0.878	1.00	92.26	C
ATOM	1050	C	SER	A	140	41.402	59.190	−0.116	1.00	85.18	C
ATOM	1051	O	SER	A	140	41.651	58.227	−0.856	1.00	79.99	O
ATOM	1052	CB	SER	A	140	43.163	58.585	1.623	1.00	98.55	C
ATOM	1053	OG	SER	A	140	42.245	57.814	2.361	1.00	95.96	O
ATOM	1054	N	PHE	A	141	40.237	59.833	−0.153	1.00	74.37	N
ATOM	1055	CA	PHE	A	141	39.186	59.412	−1.053	1.00	66.88	C
ATOM	1056	C	PHE	A	141	39.654	59.341	−2.509	1.00	68.90	C
ATOM	1057	O	PHE	A	141	39.417	58.335	−3.197	1.00	63.96	O
ATOM	1058	CB	PHE	A	141	37.936	60.300	−0.964	1.00	62.39	C
ATOM	1059	CG	PHE	A	141	36.891	59.924	−1.981	1.00	58.27	C
ATOM	1060	CD1	PHE	A	141	35.852	59.049	−1.640	1.00	52.52	C
ATOM	1061	CD2	PHE	A	141	36.997	60.368	−3.307	1.00	52.11	C
ATOM	1062	CE1	PHE	A	141	34.925	58.654	−2.584	1.00	49.74	C
ATOM	1063	CE2	PHE	A	141	36.070	59.969	−4.256	1.00	52.96	C
ATOM	1064	CZ	PHE	A	141	35.034	59.111	−3.896	1.00	51.28	C
ATOM	1065	N	ASP	A	142	40.279	60.415	−2.985	1.00	65.27	N
ATOM	1066	CA	ASP	A	142	40.682	60.464	−4.387	1.00	71.83	C
ATOM	1067	C	ASP	A	142	41.759	59.429	−4.648	1.00	75.90	C
ATOM	1068	O	ASP	A	142	41.806	58.804	−5.708	1.00	76.65	O
ATOM	1069	CB	ASP	A	142	41.195	61.848	−4.767	1.00	73.81	C
ATOM	1070	CG	ASP	A	142	40.197	62.942	−4.476	1.00	79.61	C
ATOM	1071	OD1	ASP	A	142	38.997	62.774	−4.791	1.00	85.73	O
ATOM	1072	OD2	ASP	A	142	40.619	63.979	−3.928	1.00	85.13	O
ATOM	1073	N	LEU	A	143	42.618	59.246	−3.657	1.00	77.46	N
ATOM	1074	CA	LEU	A	143	43.655	58.255	−3.730	1.00	69.74	C
ATOM	1075	C	LEU	A	143	43.051	56.873	−3.902	1.00	69.58	C
ATOM	1076	O	LEU	A	143	43.308	56.200	−4.899	1.00	74.48	O
ATOM	1077	CB	LEU	A	143	44.470	58.306	−2.464	1.00	75.28	C
ATOM	1078	CG	LEU	A	143	45.667	57.389	−2.487	1.00	83.09	C
ATOM	1079	CD1	LEU	A	143	46.437	57.614	−3.785	1.00	87.47	C
ATOM	1080	CD2	LEU	A	143	46.494	57.694	−1.248	1.00	78.07	C
ATOM	1081	N	VAL	A	144	42.243	56.451	−2.936	1.00	59.56	N
ATOM	1082	CA	VAL	A	144	41.547	55.183	−3.045	1.00	58.37	C
ATOM	1083	C	VAL	A	144	40.775	55.100	−4.370	1.00	63.24	C
ATOM	1084	O	VAL	A	144	40.594	54.019	−4.936	1.00	63.02	O
ATOM	1085	CB	VAL	A	144	40.533	55.030	−1.911	1.00	62.70	C
ATOM	1086	CG1	VAL	A	144	39.749	53.734	−2.045	1.00	61.06	C
ATOM	1087	CG2	VAL	A	144	41.221	55.093	−0.568	1.00	66.26	C
ATOM	1088	N	ALA	A	145	40.299	56.242	−4.858	1.00	60.62	N
ATOM	1089	CA	ALA	A	145	39.489	56.240	−6.056	1.00	58.41	C
ATOM	1090	C	ALA	A	145	40.369	55.827	−7.205	1.00	62.54	C
ATOM	1091	O	ALA	A	145	39.989	54.966	−7.998	1.00	68.65	O
ATOM	1092	CB	ALA	A	145	38.887	57.603	−6.300	1.00	56.03	C
ATOM	1093	N	GLN	A	146	41.558	56.430	−7.270	1.00	65.52	N
ATOM	1094	CA	GLN	A	146	42.573	56.062	−8.256	1.00	70.09	C
ATOM	1095	C	GLN	A	146	42.871	54.565	−8.243	1.00	69.66	C
ATOM	1096	O	GLN	A	146	42.876	53.925	−9.304	1.00	66.21	O
ATOM	1097	CB	GLN	A	146	43.859	56.831	−8.004	1.00	70.66	C
ATOM	1098	CG	GLN	A	146	44.797	56.821	−9.191	1.00	83.13	C
ATOM	1099	CD	GLN	A	146	46.257	56.897	−8.778	1.00	95.99	C
ATOM	1100	OE1	GLN	A	146	46.597	57.369	−7.680	1.00	94.07	O
ATOM	1101	NE2	GLN	A	146	47.135	56.419	−9.659	1.00	93.28	N
ATOM	1102	N	MET	A	147	43.092	54.016	−7.042	1.00	62.32	N
ATOM	1103	CA	MET	A	147	43.418	52.609	−6.903	1.00	68.52	C
ATOM	1104	C	MET	A	147	42.310	51.799	−7.513	1.00	71.78	C
ATOM	1105	O	MET	A	147	42.541	50.967	−8.387	1.00	81.04	O
ATOM	1106	CB	MET	A	147	43.640	52.220	−5.437	1.00	69.26	C
ATOM	1107	CG	MET	A	147	44.858	52.887	−4.796	1.00	77.91	C
ATOM	1108	SD	MET	A	147	46.350	52.737	−5.814	1.00	82.45	S
ATOM	1109	CE	MET	A	147	47.267	54.243	−5.477	1.00	76.46	C
ATOM	1110	N	ILE	A	148	41.095	52.088	−7.075	1.00	72.00	N
ATOM	1111	CA	ILE	A	148	39.913	51.412	−7.575	1.00	75.32	C
ATOM	1112	C	ILE	A	148	39.906	51.383	−9.102	1.00	78.42	C
ATOM	1113	O	ILE	A	148	39.558	50.360	−9.694	1.00	82.08	O
ATOM	1114	CB	ILE	A	148	38.627	52.041	−6.988	1.00	72.95	C
ATOM	1115	CG1	ILE	A	148	38.558	51.733	−5.491	1.00	75.65	C
ATOM	1116	CG2	ILE	A	148	37.384	51.485	−7.651	1.00	67.59	C
ATOM	1117	CD1	ILE	A	148	37.411	52.375	−4.751	1.00	75.69	C
ATOM	1118	N	ASP	A	149	40.321	52.488	−9.727	1.00	80.49	N
ATOM	1119	CA	ASP	A	149	40.346	52.583	−11.188	1.00	84.44	C
ATOM	1120	C	ASP	A	149	41.353	51.639	−11.782	1.00	86.80	C
ATOM	1121	O	ASP	A	149	41.106	51.038	−12.827	1.00	96.07	O
ATOM	1122	CB	ASP	A	149	40.679	53.994	−11.664	1.00	88.08	C
ATOM	1123	CG	ASP	A	149	39.444	54.858	−11.845	1.00	95.62	C
ATOM	1124	OD1	ASP	A	149	38.388	54.345	−12.299	1.00	90.07	O
ATOM	1125	OD2	ASP	A	149	39.540	56.064	−11.535	1.00	94.34	O
ATOM	1126	N	GLU	A	150	42.484	51.499	−11.107	1.00	83.32	N
ATOM	1127	CA	GLU	A	150	43.599	50.783	−11.683	1.00	79.84	C
ATOM	1128	C	GLU	A	150	43.552	49.270	−11.463	1.00	82.66	C
ATOM	1129	O	GLU	A	150	43.971	48.497	−12.320	1.00	85.41	O
ATOM	1130	CB	GLU	A	150	44.889	51.392	−11.186	1.00	78.07	C
ATOM	1131	CG	GLU	A	150	45.023	52.830	−11.632	1.00	86.71	C
ATOM	1132	CD	GLU	A	150	46.450	53.334	−11.594	1.00	90.75	C
ATOM	1133	OE1	GLU	A	150	47.370	52.489	−11.675	1.00	81.33	O
ATOM	1134	OE2	GLU	A	150	46.640	54.578	−11.495	1.00	91.00	O
ATOM	1135	N	ILE	A	151	43.000	48.854	−10.335	1.00	80.30	N
ATOM	1136	CA	ILE	A	151	42.987	47.457	−9.968	1.00	78.21	C
ATOM	1137	C	ILE	A	151	41.649	46.855	−10.367	1.00	79.49	C
ATOM	1138	O	ILE	A	151	40.734	46.789	−9.551	1.00	103.26	O
ATOM	1139	CB	ILE	A	151	43.252	47.318	−8.448	1.00	79.58	C
ATOM	1140	CG1	ILE	A	151	44.727	47.551	−8.139	1.00	78.52	C
ATOM	1141	CG2	ILE	A	151	42.908	45.927	−7.929	1.00	83.87	C
ATOM	1142	CD1	ILE	A	151	45.206	48.953	−8.411	1.00	92.63	C
ATOM	1143	N	LYS	A	152	41.498	46.428	−11.613	1.00	73.87	N
ATOM	1144	CA	LYS	A	152	40.183	45.928	−12.026	1.00	79.84	C
ATOM	1145	C	LYS	A	152	39.725	44.828	−11.090	1.00	78.08	C
ATOM	1146	O	LYS	A	152	40.505	43.954	−10.738	1.00	89.42	O
ATOM	1147	CB	LYS	A	152	40.158	45.484	−13.490	1.00	87.40	C
ATOM	1148	CG	LYS	A	152	39.556	46.513	−14.451	1.00	99.66	C
ATOM	1149	CD	LYS	A	152	40.237	47.884	−14.405	1.00	99.80	C
ATOM	1150	CE	LYS	A	152	39.771	48.800	−15.535	1.00	109.44	C
ATOM	1151	NZ	LYS	A	152	38.307	49.105	−15.531	1.00	113.97	N
ATOM	1152	N	MET	A	153	38.479	44.917	−10.638	1.00	75.81	N
ATOM	1153	CA	MET	A	153	37.910	43.930	−9.724	1.00	76.16	C
ATOM	1154	C	MET	A	153	36.624	43.407	−10.302	1.00	75.82	C
ATOM	1155	O	MET	A	153	36.009	44.064	−11.133	1.00	81.62	O
ATOM	1156	CB	MET	A	153	37.613	44.535	−8.366	1.00	78.27	C
ATOM	1157	CG	MET	A	153	38.787	45.246	−7.728	1.00	77.50	C
ATOM	1158	SD	MET	A	153	38.530	45.394	−5.949	1.00	79.80	S
ATOM	1159	CE	MET	A	153	39.612	46.785	−5.663	1.00	69.58	C
ATOM	1160	N	THR	A	154	36.208	42.232	−9.851	1.00	74.37	N
ATOM	1161	CA	THR	A	154	35.128	41.510	−10.510	1.00	79.19	C
ATOM	1162	C	THR	A	154	34.377	40.732	−9.452	1.00	85.61	C
ATOM	1163	O	THR	A	154	34.867	40.590	−8.329	1.00	88.21	O
ATOM	1164	CB	THR	A	154	35.675	40.461	−11.487	1.00	78.74	C
ATOM	1165	OG1	THR	A	154	35.996	39.282	−10.744	1.00	90.20	O
ATOM	1166	CG2	THR	A	154	36.943	40.937	−12.202	1.00	75.24	C
ATOM	1167	N	ASP	A	155	33.220	40.184	−9.823	1.00	90.54	N
ATOM	1168	CA	ASP	A	155	32.384	39.426	−8.887	1.00	89.44	C
ATOM	1169	C	ASP	A	155	33.126	38.269	−8.227	1.00	89.81	C
ATOM	1170	O	ASP	A	155	32.710	37.770	−7.178	1.00	92.24	O
ATOM	1171	CB	ASP	A	155	31.040	38.977	−9.510	1.00	97.59	C
ATOM	1172	CG	ASP	A	155	31.093	38.816	−11.037	1.00	104.80	C
ATOM	1173	OD1	ASP	A	155	30.539	37.812	−11.537	1.00	92.76	O
ATOM	1174	OD2	ASP	A	155	31.658	39.690	−11.737	1.00	115.45	O
ATOM	1175	N	ASP	A	156	34.241	37.866	−8.831	1.00	93.09	N
ATOM	1176	CA	ASP	A	156	35.102	36.826	−8.263	1.00	94.08	C
ATOM	1177	C	ASP	A	156	35.807	37.263	−6.976	1.00	94.05	C
ATOM	1178	O	ASP	A	156	35.826	36.521	−5.994	1.00	87.75	O
ATOM	1179	CB	ASP	A	156	36.132	36.351	−9.295	1.00	100.29	C
ATOM	1180	CG	ASP	A	156	35.496	35.565	−10.434	1.00	108.90	C
ATOM	1181	OD1	ASP	A	156	34.669	34.667	−10.148	1.00	110.14	O
ATOM	1182	OD2	ASP	A	156	35.817	35.847	−11.612	1.00	104.57	O
ATOM	1183	N	ASP	A	157	36.357	38.475	−6.975	1.00	89.58	N
ATOM	1184	CA	ASP	A	157	37.231	38.917	−5.894	1.00	78.40	C
ATOM	1185	C	ASP	A	157	36.606	39.029	−4.500	1.00	77.75	C
ATOM	1186	O	ASP	A	157	35.400	39.224	−4.358	1.00	74.84	O
ATOM	1187	CB	ASP	A	157	37.870	40.227	−6.278	1.00	73.65	C
ATOM	1188	CG	ASP	A	157	38.750	40.098	−7.475	1.00	76.03	C
ATOM	1189	OD1	ASP	A	157	39.833	39.511	−7.328	1.00	87.53	O
ATOM	1190	OD2	ASP	A	157	38.373	40.588	−8.557	1.00	82.24	O
ATOM	1191	N	LEU	A	158	37.453	38.856	−3.486	1.00	77.29	N
ATOM	1192	CA	LEU	A	158	37.154	39.241	−2.114	1.00	74.82	C
ATOM	1193	C	LEU	A	158	38.122	40.331	−1.709	1.00	80.57	C
ATOM	1194	O	LEU	A	158	39.327	40.249	−2.025	1.00	84.12	O
ATOM	1195	CB	LEU	A	158	37.317	38.087	−1.154	1.00	77.72	C
ATOM	1196	CG	LEU	A	158	36.287	36.976	−1.254	1.00	83.38	C
ATOM	1197	CD1	LEU	A	158	36.897	35.696	−0.712	1.00	76.74	C
ATOM	1198	CD2	LEU	A	158	35.032	37.356	−0.482	1.00	97.96	C
ATOM	1199	N	PHE	A	159	37.596	41.341	−1.007	1.00	70.34	N
ATOM	1200	CA	PHE	A	159	38.376	42.500	−0.637	1.00	63.38	C
ATOM	1201	C	PHE	A	159	38.449	42.669	0.864	1.00	70.47	C
ATOM	1202	O	PHE	A	159	37.458	42.439	1.567	1.00	77.67	O
ATOM	1203	CB	PHE	A	159	37.808	43.749	−1.279	1.00	62.17	C
ATOM	1204	CG	PHE	A	159	38.444	45.024	−0.797	1.00	59.96	C
ATOM	1205	CD1	PHE	A	159	39.485	45.610	−1.520	1.00	57.23	C
ATOM	1206	CD2	PHE	A	159	37.994	45.652	0.374	1.00	55.29	C
ATOM	1207	CE1	PHE	A	159	40.078	46.797	−1.073	1.00	58.08	C
ATOM	1208	CE2	PHE	A	159	38.587	46.828	0.826	1.00	56.88	C
ATOM	1209	CZ	PHE	A	159	39.630	47.405	0.101	1.00	54.70	C
ATOM	1210	N	VAL	A	160	39.630	43.083	1.337	1.00	66.97	N
ATOM	1211	CA	VAL	A	160	39.863	43.390	2.744	1.00	64.88	C
ATOM	1212	C	VAL	A	160	40.750	44.634	2.894	1.00	66.72	C
ATOM	1213	O	VAL	A	160	41.773	44.792	2.196	1.00	64.82	O
ATOM	1214	CB	VAL	A	160	40.528	42.209	3.489	1.00	61.80	C
ATOM	1215	CG1	VAL	A	160	40.844	42.576	4.926	1.00	56.63	C
ATOM	1216	CG2	VAL	A	160	39.646	40.975	3.471	1.00	71.70	C
ATOM	1217	N	ASP	A	161	40.345	45.507	3.812	1.00	65.83	N
ATOM	1218	CA	ASP	A	161	41.150	46.631	4.232	1.00	66.19	C
ATOM	1219	C	ASP	A	161	41.666	46.242	5.606	1.00	73.22	C
ATOM	1220	O	ASP	A	161	40.882	46.090	6.550	1.00	81.11	O
ATOM	1221	CB	ASP	A	161	40.301	47.905	4.300	1.00	61.21	C
ATOM	1222	CG	ASP	A	161	41.094	49.126	4.779	1.00	70.56	C
ATOM	1223	OD1	ASP	A	161	42.339	49.136	4.646	1.00	73.71	O
ATOM	1224	OD2	ASP	A	161	40.476	50.094	5.280	1.00	68.72	O
ATOM	1225	N	LEU	A	162	42.981	46.055	5.710	1.00	74.68	N
ATOM	1226	CA	LEU	A	162	43.622	45.615	6.962	1.00	71.42	C
ATOM	1227	C	LEU	A	162	43.873	46.764	7.922	1.00	71.18	C
ATOM	1228	O	LEU	A	162	44.774	47.585	7.711	1.00	71.46	O
ATOM	1229	CB	LEU	A	162	44.941	44.888	6.678	1.00	72.14	C
ATOM	1230	CG	LEU	A	162	44.824	43.640	5.802	1.00	76.17	C
ATOM	1231	CD1	LEU	A	162	46.198	43.048	5.517	1.00	72.26	C
ATOM	1232	CD2	LEU	A	162	43.901	42.621	6.453	1.00	71.92	C
ATOM	1233	N	GLY	A	163	43.100	46.792	9.000	1.00	71.30	N
ATOM	1234	CA	GLY	A	163	43.093	47.937	9.892	1.00	71.82	C
ATOM	1235	C	GLY	A	163	42.232	48.977	9.210	1.00	73.98	C
ATOM	1236	O	GLY	A	163	42.748	49.971	8.680	1.00	72.72	O
ATOM	1237	N	SER	A	164	40.921	48.728	9.217	1.00	68.32	N
ATOM	1238	CA	SER	A	164	39.982	49.472	8.384	1.00	71.28	C
ATOM	1239	C	SER	A	164	39.548	50.837	8.901	1.00	77.43	C
ATOM	1240	O	SER	A	164	38.824	51.553	8.196	1.00	74.68	O
ATOM	1241	CB	SER	A	164	38.754	48.627	8.099	1.00	70.91	C
ATOM	1242	OG	SER	A	164	38.363	47.939	9.255	1.00	76.18	O
ATOM	1243	N	GLY	A	165	40.002	51.198	10.105	1.00	80.99	N
ATOM	1244	CA	GLY	A	165	39.639	52.463	10.742	1.00	78.43	C
ATOM	1245	C	GLY	A	165	38.145	52.540	10.995	1.00	78.78	C
ATOM	1246	O	GLY	A	165	37.533	51.543	11.373	1.00	81.25	O
ATOM	1247	N	VAL	A	166	37.543	53.705	10.746	1.00	79.09	N
ATOM	1248	CA	VAL	A	166	36.093	53.858	10.952	1.00	71.99	C
ATOM	1249	C	VAL	A	166	35.325	53.238	9.790	1.00	71.09	C
ATOM	1250	O	VAL	A	166	34.100	53.216	9.821	1.00	75.79	O
ATOM	1251	CB	VAL	A	166	35.634	55.338	11.180	1.00	73.81	C
ATOM	1252	CG1	VAL	A	166	36.473	56.037	12.247	1.00	66.36	C
ATOM	1253	CG2	VAL	A	166	35.637	56.156	9.890	1.00	69.63	C
ATOM	1254	N	GLY	A	167	36.048	52.771	8.761	1.00	65.22	N
ATOM	1255	CA	GLY	A	167	35.463	51.976	7.673	1.00	59.33	C
ATOM	1256	C	GLY	A	167	35.361	52.625	6.299	1.00	62.36	C
ATOM	1257	O	GLY	A	167	34.898	51.986	5.331	1.00	60.88	O
ATOM	1258	N	GLN	A	168	35.808	53.876	6.184	1.00	55.86	N
ATOM	1259	CA	GLN	A	168	35.472	54.655	5.009	1.00	56.81	C
ATOM	1260	C	GLN	A	168	35.977	53.987	3.745	1.00	60.67	C
ATOM	1261	O	GLN	A	168	35.280	53.950	2.732	1.00	67.00	O
ATOM	1262	CB	GLN	A	168	35.946	56.099	5.123	1.00	59.92	C
ATOM	1263	CG	GLN	A	168	37.452	56.289	5.099	1.00	73.04	C
ATOM	1264	CD	GLN	A	168	38.106	56.184	6.460	1.00	73.42	C
ATOM	1265	OE1	GLN	A	168	37.754	55.345	7.294	1.00	79.82	O
ATOM	1266	NE2	GLN	A	168	39.080	57.039	6.685	1.00	80.58	N
ATOM	1267	N	VAL	A	169	37.173	53.423	3.806	1.00	59.60	N
ATOM	1268	CA	VAL	A	169	37.735	52.814	2.609	1.00	61.00	C
ATOM	1269	C	VAL	A	169	36.967	51.576	2.173	1.00	60.45	C
ATOM	1270	O	VAL	A	169	36.713	51.392	0.984	1.00	59.15	O
ATOM	1271	CB	VAL	A	169	39.221	52.510	2.771	1.00	65.65	C
ATOM	1272	CG1	VAL	A	169	39.693	51.597	1.651	1.00	64.42	C
ATOM	1273	CG2	VAL	A	169	40.013	53.817	2.783	1.00	60.59	C
ATOM	1274	N	VAL	A	170	36.575	50.745	3.133	1.00	59.05	N
ATOM	1275	CA	VAL	A	170	35.748	49.588	2.826	1.00	61.79	C
ATOM	1276	C	VAL	A	170	34.461	50.039	2.150	1.00	67.67	C
ATOM	1277	O	VAL	A	170	34.039	49.459	1.139	1.00	65.28	O
ATOM	1278	CB	VAL	A	170	35.374	48.815	4.092	1.00	64.91	C
ATOM	1279	CG1	VAL	A	170	34.435	47.655	3.761	1.00	62.25	C
ATOM	1280	CG2	VAL	A	170	36.628	48.343	4.806	1.00	66.63	C
ATOM	1281	N	LEU	A	171	33.840	51.082	2.705	1.00	68.20	N
ATOM	1282	CA	LEU	A	171	32.592	51.582	2.146	1.00	64.49	C
ATOM	1283	C	LEU	A	171	32.832	52.119	0.737	1.00	62.51	C
ATOM	1284	O	LEU	A	171	32.054	51.843	−0.192	1.00	60.13	O
ATOM	1285	CB	LEU	A	171	31.985	52.661	3.034	1.00	69.75	C
ATOM	1286	CG	LEU	A	171	31.573	52.359	4.480	1.00	69.28	C
ATOM	1287	CD1	LEU	A	171	31.120	53.641	5.162	1.00	62.60	C
ATOM	1288	CD2	LEU	A	171	30.466	51.320	4.551	1.00	68.42	C
ATOM	1289	N	GLN	A	172	33.923	52.853	0.559	1.00	53.42	N
ATOM	1290	CA	GLN	A	172	34.209	53.373	−0.772	1.00	57.63	C
ATOM	1291	C	GLN	A	172	34.311	52.226	−1.791	1.00	64.84	C
ATOM	1292	O	GLN	A	172	33.670	52.270	−2.852	1.00	61.73	O
ATOM	1293	CB	GLN	A	172	35.463	54.258	−0.781	1.00	51.11	C
ATOM	1294	CG	GLN	A	172	35.786	54.840	−2.141	1.00	47.82	C
ATOM	1295	CD	GLN	A	172	36.844	55.926	−2.090	1.00	54.28	C
ATOM	1296	OE1	GLN	A	172	37.351	56.262	−1.034	1.00	54.69	O
ATOM	1297	NE2	GLN	A	172	37.168	56.496	−3.245	1.00	60.46	N
ATOM	1298	N	VAL	A	173	35.082	51.185	−1.463	1.00	64.98	N
ATOM	1299	CA	VAL	A	173	35.287	50.118	−2.437	1.00	61.88	C
ATOM	1300	C	VAL	A	173	34.001	49.366	−2.683	1.00	60.74	C
ATOM	1301	O	VAL	A	173	33.674	49.066	−3.838	1.00	58.99	O
ATOM	1302	CB	VAL	A	173	36.406	49.133	−2.065	1.00	59.66	C
ATOM	1303	CG1	VAL	A	173	36.472	48.037	−3.111	1.00	55.29	C
ATOM	1304	CG2	VAL	A	173	37.741	49.853	−2.008	1.00	58.02	C
ATOM	1305	N	ALA	A	174	33.279	49.068	−1.603	1.00	58.37	N
ATOM	1306	CA	ALA	A	174	32.031	48.312	−1.721	1.00	64.08	C
ATOM	1307	C	ALA	A	174	31.036	49.047	−2.606	1.00	71.83	C
ATOM	1308	O	ALA	A	174	30.258	48.415	−3.333	1.00	73.06	O
ATOM	1309	CB	ALA	A	174	31.423	48.045	−0.359	1.00	62.11	C
ATOM	1310	N	ALA	A	175	31.076	50.384	−2.543	1.00	70.21	N
ATOM	1311	CA	ALA	A	175	30.185	51.217	−3.346	1.00	66.66	C
ATOM	1312	C	ALA	A	175	30.629	51.221	−4.780	1.00	68.06	C
ATOM	1313	O	ALA	A	175	29.815	51.291	−5.673	1.00	81.13	O
ATOM	1314	CB	ALA	A	175	30.152	52.631	−2.812	1.00	70.03	C
ATOM	1315	N	ALA	A	176	31.933	51.115	−4.997	1.00	72.21	N
ATOM	1316	CA	ALA	A	176	32.508	51.275	−6.325	1.00	65.10	C
ATOM	1317	C	ALA	A	176	32.622	49.992	−7.153	1.00	66.15	C
ATOM	1318	O	ALA	A	176	32.628	50.062	−8.377	1.00	69.05	O
ATOM	1319	CB	ALA	A	176	33.857	51.949	−6.213	1.00	60.36	C
ATOM	1320	N	THR	A	177	32.694	48.833	−6.500	1.00	69.60	N
ATOM	1321	CA	THR	A	177	33.010	47.563	−7.190	1.00	69.90	C
ATOM	1322	C	THR	A	177	31.979	46.481	−6.939	1.00	73.92	C
ATOM	1323	O	THR	A	177	31.082	46.622	−6.113	1.00	77.96	O
ATOM	1324	CB	THR	A	177	34.373	46.983	−6.740	1.00	65.08	C
ATOM	1325	OG1	THR	A	177	34.236	46.360	−5.442	1.00	61.25	O
ATOM	1326	CG2	THR	A	177	35.417	48.075	−6.687	1.00	54.60	C
ATOM	1327	N	ASN	A	178	32.154	45.370	−7.627	1.00	83.01	N
ATOM	1328	CA	ASN	A	178	31.211	44.278	−7.539	1.00	89.84	C
ATOM	1329	C	ASN	A	178	31.844	43.007	−6.977	1.00	83.77	C
ATOM	1330	O	ASN	A	178	31.465	41.913	−7.358	1.00	88.74	O
ATOM	1331	CB	ASN	A	178	30.621	44.015	−8.926	1.00	100.25	C
ATOM	1332	CG	ASN	A	178	31.693	43.762	−9.971	1.00	113.04	C
ATOM	1333	OD1	ASN	A	178	32.708	44.470	−10.028	1.00	117.99	O
ATOM	1334	ND2	ASN	A	178	31.481	42.743	−10.801	1.00	121.14	N
ATOM	1335	N	CYS	A	179	32.805	43.147	−6.073	1.00	76.61	N
ATOM	1336	CA	CYS	A	179	33.328	41.988	−5.353	1.00	80.22	C
ATOM	1337	C	CYS	A	179	32.184	41.233	−4.657	1.00	86.33	C
ATOM	1338	O	CYS	A	179	31.165	41.828	−4.291	1.00	81.49	O
ATOM	1339	CB	CYS	A	179	34.410	42.398	−4.336	1.00	74.17	C
ATOM	1340	SG	CYS	A	179	35.814	43.290	−5.064	1.00	87.83	S
ATOM	1341	N	LYS	A	180	32.359	39.920	−4.491	1.00	90.58	N
ATOM	1342	CA	LYS	A	180	31.393	39.074	−3.799	1.00	87.35	C
ATOM	1343	C	LYS	A	180	31.241	39.537	−2.346	1.00	90.45	C
ATOM	1344	O	LYS	A	180	30.226	39.267	−1.696	1.00	102.13	O
ATOM	1345	CB	LYS	A	180	31.852	37.608	−3.868	1.00	101.07	C
ATOM	1346	CG	LYS	A	180	30.776	36.555	−3.597	1.00	118.50	C
ATOM	1347	CD	LYS	A	180	30.772	36.066	−2.148	1.00	121.62	C
ATOM	1348	CE	LYS	A	180	29.558	35.195	−1.846	1.00	124.55	C
ATOM	1349	NZ	LYS	A	180	29.658	33.825	−2.432	1.00	123.66	N
ATOM	1350	N	HIS	A	181	32.252	40.235	−1.840	1.00	85.17	N
ATOM	1351	CA	HIS	A	181	32.226	40.732	−0.470	1.00	83.61	C
ATOM	1352	C	HIS	A	181	33.421	41.594	−0.142	1.00	84.18	C
ATOM	1353	O	HIS	A	181	34.503	41.410	−0.702	1.00	85.96	O
ATOM	1354	CB	HIS	A	181	32.146	39.573	0.502	1.00	81.88	C
ATOM	1355	CG	HIS	A	181	31.364	39.885	1.728	1.00	82.98	C
ATOM	1356	ND1	HIS	A	181	30.023	39.888	1.739	1.00	90.45	N
ATOM	1357	CD2	HIS	A	181	31.774	40.242	3.008	1.00	81.30	C
ATOM	1358	CE1	HIS	A	181	29.589	40.218	2.976	1.00	92.38	C
ATOM	1359	NE2	HIS	A	181	30.664	40.431	3.750	1.00	85.50	N
ATOM	1360	N	HIS	A	182	33.232	42.552	0.763	1.00	72.66	N
ATOM	1361	CA	HIS	A	182	34.306	43.447	1.161	1.00	67.31	C
ATOM	1362	C	HIS	A	182	34.389	43.362	2.631	1.00	65.42	C
ATOM	1363	O	HIS	A	182	33.375	43.177	3.288	1.00	71.76	O
ATOM	1364	CB	HIS	A	182	34.006	44.882	0.749	1.00	64.71	C
ATOM	1365	CG	HIS	A	182	33.815	45.072	−0.738	1.00	62.30	C
ATOM	1366	ND1	HIS	A	182	32.726	44.620	−1.395	1.00	66.02	N
ATOM	1367	CD2	HIS	A	182	34.612	45.709	−1.691	1.00	63.14	C
ATOM	1368	CE1	HIS	A	182	32.823	44.949	−2.706	1.00	69.62	C
ATOM	1369	NE2	HIS	A	182	33.973	45.617	−2.887	1.00	62.86	N
ATOM	1370	N	TYR	A	183	35.587	43.477	3.183	1.00	64.74	N
ATOM	1371	CA	TYR	A	183	35.727	43.330	4.623	1.00	70.95	C
ATOM	1372	C	TYR	A	183	36.624	44.389	5.162	1.00	71.02	C
ATOM	1373	O	TYR	A	183	37.618	44.756	4.535	1.00	76.94	O
ATOM	1374	CB	TYR	A	183	36.360	41.990	4.996	1.00	71.76	C
ATOM	1375	CG	TYR	A	183	35.551	40.786	4.658	1.00	72.85	C
ATOM	1376	CD1	TYR	A	183	35.628	40.207	3.398	1.00	73.45	C
ATOM	1377	CD2	TYR	A	183	34.709	40.206	5.604	1.00	80.17	C
ATOM	1378	CE1	TYR	A	183	34.877	39.084	3.078	1.00	82.01	C
ATOM	1379	CE2	TYR	A	183	33.961	39.074	5.302	1.00	78.78	C
ATOM	1380	CZ	TYR	A	183	34.047	38.517	4.039	1.00	81.10	C
ATOM	1381	OH	TYR	A	183	33.296	37.405	3.725	1.00	85.27	O
ATOM	1382	N	GLY	A	184	36.298	44.841	6.356	1.00	67.59	N
ATOM	1383	CA	GLY	A	184	37.218	45.649	7.121	1.00	72.28	C
ATOM	1384	C	GLY	A	184	37.441	44.965	8.442	1.00	76.51	C
ATOM	1385	O	GLY	A	184	36.537	44.317	8.985	1.00	77.95	O
ATOM	1386	N	VAL	A	185	38.654	45.090	8.954	1.00	77.16	N
ATOM	1387	CA	VAL	A	185	38.992	44.485	10.226	1.00	76.95	C
ATOM	1388	C	VAL	A	185	39.773	45.525	11.006	1.00	79.94	C
ATOM	1389	O	VAL	A	185	40.722	46.117	10.495	1.00	73.76	O
ATOM	1390	CB	VAL	A	185	39.750	43.143	10.054	1.00	76.17	C
ATOM	1391	CG1	VAL	A	185	40.991	43.305	9.185	1.00	72.25	C
ATOM	1392	CG2	VAL	A	185	40.109	42.549	11.407	1.00	79.24	C
ATOM	1393	N	GLU	A	186	39.317	45.766	12.232	1.00	87.17	N
ATOM	1394	CA	GLU	A	186	39.827	46.833	13.089	1.00	90.04	C
ATOM	1395	C	GLU	A	186	39.977	46.305	14.518	1.00	94.44	C
ATOM	1396	O	GLU	A	186	39.079	45.622	15.031	1.00	91.36	O
ATOM	1397	CB	GLU	A	186	38.852	48.011	13.053	1.00	82.54	C
ATOM	1398	CG	GLU	A	186	39.146	49.125	14.032	1.00	78.40	C
ATOM	1399	CD	GLU	A	186	40.495	49.740	13.796	1.00	82.12	C
ATOM	1400	OE1	GLU	A	186	41.247	49.875	14.771	1.00	85.52	O
ATOM	1401	OE2	GLU	A	186	40.806	50.076	12.635	1.00	87.86	O
ATOM	1402	N	LYS	A	187	41.105	46.609	15.153	1.00	89.80	N
ATOM	1403	CA	LYS	A	187	41.352	46.092	16.496	1.00	94.87	C
ATOM	1404	C	LYS	A	187	40.882	47.071	17.558	1.00	94.56	C
ATOM	1405	O	LYS	A	187	39.963	46.760	18.304	1.00	107.03	O
ATOM	1406	CB	LYS	A	187	42.814	45.640	16.702	1.00	93.00	C
ATOM	1407	CG	LYS	A	187	43.877	46.716	16.515	1.00	94.75	C
ATOM	1408	CD	LYS	A	187	45.270	46.201	16.839	1.00	94.31	C
ATOM	1409	CE	LYS	A	187	46.271	47.348	16.931	1.00	91.47	C
ATOM	1410	NZ	LYS	A	187	47.470	46.960	17.730	1.00	101.50	N
ATOM	1411	N	ALA	A	188	41.491	48.258	17.591	1.00	97.17	N
ATOM	1412	CA	ALA	A	188	41.142	49.339	18.523	1.00	94.38	C
ATOM	1413	C	ALA	A	188	39.635	49.539	18.622	1.00	105.18	C
ATOM	1414	O	ALA	A	188	38.911	49.461	17.622	1.00	104.53	O
ATOM	1415	CB	ALA	A	188	41.819	50.636	18.114	1.00	80.99	C
ATOM	1416	N	ASP	A	189	39.170	49.807	19.838	1.00	116.25	N
ATOM	1417	CA	ASP	A	189	37.742	49.780	20.132	1.00	111.68	C
ATOM	1418	C	ASP	A	189	36.984	51.015	19.696	1.00	102.49	C
ATOM	1419	O	ASP	A	189	35.860	50.899	19.203	1.00	97.38	O
ATOM	1420	CB	ASP	A	189	37.515	49.500	21.611	1.00	120.96	C
ATOM	1421	CG	ASP	A	189	37.996	48.120	22.005	1.00	138.24	C
ATOM	1422	OD1	ASP	A	189	37.417	47.132	21.504	1.00	134.67	O
ATOM	1423	OD2	ASP	A	189	38.959	48.023	22.796	1.00	145.12	O
ATOM	1424	N	ILE	A	190	37.584	52.191	19.866	1.00	94.01	N
ATOM	1425	CA	ILE	A	190	36.853	53.417	19.555	1.00	95.21	C
ATOM	1426	C	ILE	A	190	36.545	53.553	18.042	1.00	98.09	C
ATOM	1427	O	ILE	A	190	35.391	53.808	17.679	1.00	104.71	O
ATOM	1428	CB	ILE	A	190	37.391	54.709	20.276	1.00	95.72	C
ATOM	1429	CG1	ILE	A	190	38.336	55.536	19.413	1.00	97.11	C
ATOM	1430	CG2	ILE	A	190	38.012	54.403	21.639	1.00	96.07	C
ATOM	1431	CD1	ILE	A	190	37.606	56.509	18.525	1.00	97.28	C
ATOM	1432	N	PRO	A	191	37.545	53.337	17.154	1.00	95.75	N
ATOM	1433	CA	PRO	A	191	37.175	53.388	15.738	1.00	83.50	C
ATOM	1434	C	PRO	A	191	36.196	52.285	15.335	1.00	80.28	C
ATOM	1435	O	PRO	A	191	35.314	52.518	14.524	1.00	82.92	O
ATOM	1436	CB	PRO	A	191	38.514	53.237	15.019	1.00	79.71	C
ATOM	1437	CG	PRO	A	191	39.399	52.566	15.996	1.00	83.06	C
ATOM	1438	CD	PRO	A	191	38.997	53.135	17.318	1.00	89.62	C
ATOM	1439	N	ALA	A	192	36.342	51.096	15.906	1.00	85.58	N
ATOM	1440	CA	ALA	A	192	35.379	50.023	15.670	1.00	86.66	C
ATOM	1441	C	ALA	A	192	33.960	50.458	16.052	1.00	89.12	C
ATOM	1442	O	ALA	A	192	32.993	50.136	15.351	1.00	90.45	O
ATOM	1443	CB	ALA	A	192	35.785	48.772	16.428	1.00	82.67	C
ATOM	1444	N	LYS	A	193	33.850	51.190	17.163	1.00	92.07	N
ATOM	1445	CA	LYS	A	193	32.584	51.785	17.579	1.00	96.60	C
ATOM	1446	C	LYS	A	193	32.073	52.721	16.478	1.00	89.98	C
ATOM	1447	O	LYS	A	193	31.023	52.465	15.890	1.00	84.21	O
ATOM	1448	CB	LYS	A	193	32.727	52.508	18.938	1.00	107.12	C
ATOM	1449	CG	LYS	A	193	31.556	53.405	19.364	1.00	114.24	C
ATOM	1450	CD	LYS	A	193	30.205	52.707	19.245	1.00	118.51	C
ATOM	1451	CE	LYS	A	193	29.102	53.509	19.906	1.00	121.55	C
ATOM	1452	NZ	LYS	A	193	28.959	53.117	21.336	1.00	121.19	N
ATOM	1453	N	TYR	A	194	32.824	53.782	16.184	1.00	82.19	N
ATOM	1454	CA	TYR	A	194	32.473	54.668	15.083	1.00	80.44	C
ATOM	1455	C	TYR	A	194	32.048	53.926	13.807	1.00	78.79	C
ATOM	1456	O	TYR	A	194	31.079	54.311	13.159	1.00	82.09	O
ATOM	1457	CB	TYR	A	194	33.606	55.626	14.792	1.00	78.30	C
ATOM	1458	CG	TYR	A	194	33.672	56.789	15.748	1.00	95.29	C
ATOM	1459	CD1	TYR	A	194	32.502	57.367	16.272	1.00	105.52	C
ATOM	1460	CD2	TYR	A	194	34.898	57.348	16.105	1.00	103.39	C
ATOM	1461	CE1	TYR	A	194	32.560	58.452	17.143	1.00	108.82	C
ATOM	1462	CE2	TYR	A	194	34.968	58.434	16.973	1.00	111.55	C
ATOM	1463	CZ	TYR	A	194	33.803	58.980	17.493	1.00	112.55	C
ATOM	1464	OH	TYR	A	194	33.891	60.054	18.350	1.00	117.17	O
ATOM	1465	N	ALA	A	195	32.735	52.833	13.489	1.00	77.40	N
ATOM	1466	CA	ALA	A	195	32.462	52.074	12.275	1.00	78.17	C
ATOM	1467	C	ALA	A	195	31.048	51.547	12.238	1.00	80.06	C
ATOM	1468	O	ALA	A	195	30.436	51.474	11.167	1.00	83.33	O
ATOM	1469	CB	ALA	A	195	33.454	50.941	12.106	1.00	83.72	C
ATOM	1470	N	GLU	A	196	30.525	51.188	13.406	1.00	78.67	N
ATOM	1471	CA	GLU	A	196	29.134	50.764	13.502	1.00	78.32	C
ATOM	1472	C	GLU	A	196	28.170	51.844	13.049	1.00	78.67	C
ATOM	1473	O	GLU	A	196	27.212	51.567	12.320	1.00	80.48	O
ATOM	1474	CB	GLU	A	196	28.799	50.368	14.915	1.00	78.80	C
ATOM	1475	CG	GLU	A	196	29.237	48.973	15.275	1.00	85.66	C
ATOM	1476	CD	GLU	A	196	28.916	48.657	16.712	1.00	93.43	C
ATOM	1477	OE1	GLU	A	196	27.783	48.957	17.163	1.00	97.37	O
ATOM	1478	OE2	GLU	A	196	29.809	48.121	17.392	1.00	98.57	O
ATOM	1479	N	THR	A	197	28.425	53.077	13.472	1.00	74.62	N
ATOM	1480	CA	THR	A	197	27.569	54.168	13.052	1.00	81.13	C
ATOM	1481	C	THR	A	197	27.779	54.476	11.583	1.00	84.28	C
ATOM	1482	O	THR	A	197	26.809	54.650	10.834	1.00	86.91	O
ATOM	1483	CB	THR	A	197	27.789	55.418	13.899	1.00	83.11	C
ATOM	1484	OG1	THR	A	197	27.570	55.075	15.269	1.00	93.05	O
ATOM	1485	CG2	THR	A	197	26.807	56.517	13.493	1.00	76.32	C
ATOM	1486	N	MET	A	198	29.047	54.536	11.178	1.00	79.98	N
ATOM	1487	CA	MET	A	198	29.390	54.725	9.776	1.00	77.85	C
ATOM	1488	C	MET	A	198	28.565	53.734	8.972	1.00	75.52	C
ATOM	1489	O	MET	A	198	27.926	54.093	7.985	1.00	68.26	O
ATOM	1490	CB	MET	A	198	30.874	54.466	9.537	1.00	73.04	C
ATOM	1491	CG	MET	A	198	31.814	55.522	10.096	1.00	74.96	C
ATOM	1492	SD	MET	A	198	31.809	57.126	9.268	1.00	77.00	S
ATOM	1493	CE	MET	A	198	32.071	56.689	7.553	1.00	66.32	C
ATOM	1494	N	ASP	A	199	28.552	52.490	9.433	1.00	74.65	N
ATOM	1495	CA	ASP	A	199	27.871	51.448	8.708	1.00	77.70	C
ATOM	1496	C	ASP	A	199	26.396	51.789	8.563	1.00	79.72	C
ATOM	1497	O	ASP	A	199	25.851	51.702	7.465	1.00	76.28	O
ATOM	1498	CB	ASP	A	199	28.077	50.094	9.386	1.00	78.97	C
ATOM	1499	CG	ASP	A	199	27.204	49.010	8.790	1.00	88.12	C
ATOM	1500	OD1	ASP	A	199	27.083	48.922	7.549	1.00	87.81	O
ATOM	1501	OD2	ASP	A	199	26.622	48.242	9.577	1.00	100.82	O
ATOM	1502	N	ARG	A	200	25.765	52.192	9.670	1.00	87.18	N
ATOM	1503	CA	ARG	A	200	24.340	52.535	9.674	1.00	81.32	C
ATOM	1504	C	ARG	A	200	24.078	53.727	8.760	1.00	79.40	C
ATOM	1505	O	ARG	A	200	23.300	53.625	7.807	1.00	83.12	O
ATOM	1506	CB	ARG	A	200	23.853	52.814	11.093	1.00	85.62	C
ATOM	1507	CG	ARG	A	200	23.383	51.580	11.844	1.00	97.82	C
ATOM	1508	CD	ARG	A	200	22.765	51.928	13.196	1.00	105.97	C
ATOM	1509	NE	ARG	A	200	23.775	52.086	14.249	1.00	115.59	N
ATOM	1510	CZ	ARG	A	200	24.136	53.246	14.803	1.00	119.27	C
ATOM	1511	NH1	ARG	A	200	25.071	53.259	15.746	1.00	113.86	N
ATOM	1512	NH2	ARG	A	200	23.573	54.394	14.430	1.00	116.05	N
ATOM	1513	N	GLU	A	201	24.760	54.838	9.038	1.00	72.33	N
ATOM	1514	CA	GLU	A	201	24.657	56.049	8.238	1.00	72.07	C
ATOM	1515	C	GLU	A	201	24.804	55.780	6.747	1.00	74.85	C
ATOM	1516	O	GLU	A	201	24.030	56.282	5.927	1.00	74.68	O
ATOM	1517	CB	GLU	A	201	25.709	57.061	8.684	1.00	76.50	C
ATOM	1518	CG	GLU	A	201	25.288	57.928	9.867	1.00	82.47	C
ATOM	1519	CD	GLU	A	201	23.890	58.501	9.712	1.00	81.32	C
ATOM	1520	OE1	GLU	A	201	23.651	59.306	8.775	1.00	77.10	O
ATOM	1521	OE2	GLU	A	201	23.026	58.120	10.528	1.00	85.88	O
ATOM	1522	N	PHE	A	202	25.793	54.967	6.400	1.00	74.00	N
ATOM	1523	CA	PHE	A	202	26.016	54.623	5.014	1.00	70.89	C
ATOM	1524	C	PHE	A	202	24.817	53.930	4.392	1.00	70.66	C
ATOM	1525	O	PHE	A	202	24.417	54.273	3.277	1.00	72.85	O
ATOM	1526	CB	PHE	A	202	27.266	53.768	4.850	1.00	70.27	C
ATOM	1527	CG	PHE	A	202	27.612	53.466	3.415	1.00	66.51	C
ATOM	1528	CD1	PHE	A	202	28.081	54.473	2.568	1.00	66.58	C
ATOM	1529	CD2	PHE	A	202	27.481	52.185	2.917	1.00	61.36	C
ATOM	1530	CE1	PHE	A	202	28.407	54.210	1.249	1.00	61.69	C
ATOM	1531	CE2	PHE	A	202	27.812	51.907	1.605	1.00	67.47	C
ATOM	1532	CZ	PHE	A	202	28.275	52.922	0.767	1.00	69.94	C
ATOM	1533	N	ARG	A	203	24.241	52.961	5.099	1.00	67.76	N
ATOM	1534	CA	ARG	A	203	23.141	52.187	4.523	1.00	71.93	C
ATOM	1535	C	ARG	A	203	21.952	53.115	4.275	1.00	76.16	C
ATOM	1536	O	ARG	A	203	21.305	53.054	3.214	1.00	74.63	O
ATOM	1537	CB	ARG	A	203	22.768	50.984	5.406	1.00	78.63	C
ATOM	1538	CG	ARG	A	203	23.937	50.036	5.683	1.00	85.67	C
ATOM	1539	CD	ARG	A	203	23.524	48.606	6.004	1.00	87.89	C
ATOM	1540	NE	ARG	A	203	24.692	47.713	5.999	1.00	100.09	N
ATOM	1541	CZ	ARG	A	203	24.999	46.842	5.030	1.00	102.60	C
ATOM	1542	NH1	ARG	A	203	24.223	46.710	3.960	1.00	110.73	N
ATOM	1543	NH2	ARG	A	203	26.088	46.088	5.125	1.00	99.74	N
ATOM	1544	N	LYS	A	204	21.719	54.007	5.242	1.00	70.86	N
ATOM	1545	CA	LYS	A	204	20.617	54.946	5.209	1.00	67.95	C
ATOM	1546	C	LYS	A	204	20.758	55.887	4.017	1.00	72.65	C
ATOM	1547	O	LYS	A	204	19.832	56.033	3.221	1.00	78.31	O
ATOM	1548	CB	LYS	A	204	20.569	55.724	6.531	1.00	72.43	C
ATOM	1549	CG	LYS	A	204	19.670	56.960	6.537	1.00	70.88	C
ATOM	1550	CD	LYS	A	204	19.214	57.314	7.943	1.00	78.67	C
ATOM	1551	CE	LYS	A	204	20.306	57.915	8.827	1.00	89.54	C
ATOM	1552	NZ	LYS	A	204	20.665	59.323	8.472	1.00	92.72	N
ATOM	1553	N	TRP	A	205	21.919	56.520	3.883	1.00	68.14	N
ATOM	1554	CA	TRP	A	205	22.112	57.483	2.799	1.00	69.09	C
ATOM	1555	C	TRP	A	205	22.074	56.860	1.430	1.00	69.66	C
ATOM	1556	O	TRP	A	205	21.606	57.481	0.475	1.00	71.50	O
ATOM	1557	CB	TRP	A	205	23.377	58.315	3.013	1.00	64.43	C
ATOM	1558	CG	TRP	A	205	23.196	59.360	4.095	1.00	65.07	C
ATOM	1559	CD1	TRP	A	205	23.667	59.328	5.403	1.00	64.70	C
ATOM	1560	CD2	TRP	A	205	22.441	60.613	3.995	1.00	65.40	C
ATOM	1561	NE1	TRP	A	205	23.288	60.448	6.086	1.00	64.40	N
ATOM	1562	CE2	TRP	A	205	22.545	61.258	5.298	1.00	65.08	C
ATOM	1563	CE3	TRP	A	205	21.706	61.236	2.989	1.00	67.86	C
ATOM	1564	CZ2	TRP	A	205	21.943	62.476	5.559	1.00	68.19	C
ATOM	1565	CZ3	TRP	A	205	21.100	62.457	3.267	1.00	65.75	C
ATOM	1566	CH2	TRP	A	205	21.223	63.067	4.516	1.00	62.40	C
ATOM	1567	N	MET	A	206	22.540	55.621	1.319	1.00	67.52	N
ATOM	1568	CA	MET	A	206	22.519	54.944	0.042	1.00	66.40	C
ATOM	1569	C	MET	A	206	21.081	54.622	−0.371	1.00	70.67	C
ATOM	1570	O	MET	A	206	20.721	54.763	−1.546	1.00	65.42	O
ATOM	1571	CB	MET	A	206	23.394	53.697	0.089	1.00	73.45	C
ATOM	1572	CG	MET	A	206	24.892	53.982	0.085	1.00	75.94	C
ATOM	1573	SD	MET	A	206	25.548	54.539	−1.507	1.00	74.34	S
ATOM	1574	CE	MET	A	206	25.690	53.000	−2.388	1.00	76.03	C
ATOM	1575	N	LYS	A	207	20.259	54.211	0.600	1.00	70.40	N
ATOM	1576	CA	LYS	A	207	18.825	54.031	0.362	1.00	74.40	C
ATOM	1577	C	LYS	A	207	18.175	55.364	−0.058	1.00	74.47	C
ATOM	1578	O	LYS	A	207	17.433	55.447	−1.041	1.00	74.19	O
ATOM	1579	CB	LYS	A	207	18.139	53.434	1.600	1.00	82.03	C
ATOM	1580	CG	LYS	A	207	18.309	51.921	1.759	1.00	94.80	C
ATOM	1581	CD	LYS	A	207	17.658	51.162	0.590	1.00	114.67	C
ATOM	1582	CE	LYS	A	207	17.933	49.661	0.591	1.00	114.07	C
ATOM	1583	NZ	LYS	A	207	17.471	48.987	1.841	1.00	127.27	N
ATOM	1584	N	TRP	A	208	18.510	56.416	0.672	1.00	70.71	N
ATOM	1585	CA	TRP	A	208	18.005	57.747	0.391	1.00	64.65	C
ATOM	1586	C	TRP	A	208	18.231	58.198	−1.018	1.00	65.14	C
ATOM	1587	O	TRP	A	208	17.323	58.747	−1.629	1.00	69.42	O
ATOM	1588	CB	TRP	A	208	18.620	58.729	1.360	1.00	59.99	C
ATOM	1589	CG	TRP	A	208	17.912	60.053	1.415	1.00	64.54	C
ATOM	1590	CD1	TRP	A	208	16.930	60.460	2.322	1.00	68.30	C
ATOM	1591	CD2	TRP	A	208	18.134	61.214	0.557	1.00	65.09	C
ATOM	1592	NE1	TRP	A	208	16.550	61.754	2.085	1.00	62.01	N
ATOM	1593	CE2	TRP	A	208	17.229	62.266	1.046	1.00	62.98	C
ATOM	1594	CE3	TRP	A	208	18.962	61.484	−0.526	1.00	66.11	C
ATOM	1595	CZ2	TRP	A	208	17.165	63.515	0.449	1.00	63.76	C
ATOM	1596	CZ3	TRP	A	208	18.889	62.751	−1.117	1.00	65.40	C
ATOM	1597	CH2	TRP	A	208	18.007	63.738	−0.641	1.00	63.65	C
ATOM	1598	N	TYR	A	209	19.436	57.997	−1.552	1.00	67.05	N
ATOM	1599	CA	TYR	A	209	19.703	58.401	−2.939	1.00	66.05	C
ATOM	1600	C	TYR	A	209	19.297	57.264	−3.879	1.00	65.33	C
ATOM	1601	O	TYR	A	209	19.403	57.395	−5.097	1.00	61.49	O
ATOM	1602	CB	TYR	A	209	21.184	58.745	−3.170	1.00	64.71	C
ATOM	1603	CG	TYR	A	209	21.754	59.954	−2.431	1.00	59.31	C
ATOM	1604	CD1	TYR	A	209	21.784	61.233	−3.030	1.00	54.95	C
ATOM	1605	CD2	TYR	A	209	22.328	59.809	−1.171	1.00	54.84	C
ATOM	1606	CE1	TYR	A	209	22.322	62.334	−2.370	1.00	47.80	C
ATOM	1607	CE2	TYR	A	209	22.879	60.892	−0.506	1.00	55.91	C
ATOM	1608	CZ	TYR	A	209	22.879	62.151	−1.104	1.00	55.61	C
ATOM	1609	OH	TYR	A	209	23.431	63.209	−0.405	1.00	55.70	O
ATOM	1610	N	GLY	A	210	18.843	56.146	−3.312	1.00	60.23	N
ATOM	1611	CA	GLY	A	210	18.481	54.987	−4.122	1.00	65.87	C
ATOM	1612	C	GLY	A	210	19.613	54.429	−4.977	1.00	70.56	C
ATOM	1613	O	GLY	A	210	19.420	54.158	−6.171	1.00	75.15	O
ATOM	1614	N	LYS	A	211	20.790	54.265	−4.363	1.00	66.61	N
ATOM	1615	CA	LYS	A	211	21.985	53.746	−5.030	1.00	61.73	C
ATOM	1616	C	LYS	A	211	22.485	52.449	−4.388	1.00	72.08	C
ATOM	1617	O	LYS	A	211	22.490	52.308	−3.155	1.00	72.86	O
ATOM	1618	CB	LYS	A	211	23.091	54.786	−5.024	1.00	58.67	C
ATOM	1619	CG	LYS	A	211	22.816	56.006	−5.876	1.00	61.14	C
ATOM	1620	CD	LYS	A	211	22.777	55.642	−7.352	1.00	63.41	C
ATOM	1621	CE	LYS	A	211	23.023	56.851	−8.234	1.00	70.83	C
ATOM	1622	NZ	LYS	A	211	22.544	56.658	−9.632	1.00	75.54	N
ATOM	1623	N	LYS	A	212	22.923	51.526	−5.244	1.00	76.77	N
ATOM	1624	CA	LYS	A	212	23.275	50.143	−4.897	1.00	79.60	C
ATOM	1625	C	LYS	A	212	24.704	50.006	−4.315	1.00	75.41	C
ATOM	1626	O	LYS	A	212	25.584	50.805	−4.617	1.00	76.61	O
ATOM	1627	CB	LYS	A	212	23.131	49.327	−6.194	1.00	88.57	C
ATOM	1628	CG	LYS	A	212	23.537	47.863	−6.177	1.00	98.58	C
ATOM	1629	CD	LYS	A	212	24.229	47.523	−7.496	1.00	109.02	C
ATOM	1630	CE	LYS	A	212	23.870	46.135	−8.018	1.00	119.03	C
ATOM	1631	NZ	LYS	A	212	23.861	45.070	−6.971	1.00	121.53	N
ATOM	1632	N	HIS	A	213	24.941	48.985	−3.499	1.00	77.91	N
ATOM	1633	CA	HIS	A	213	26.305	48.670	−3.070	1.00	81.34	C
ATOM	1634	C	HIS	A	213	26.562	47.195	−2.902	1.00	85.40	C
ATOM	1635	O	HIS	A	213	25.668	46.433	−2.531	1.00	91.73	O
ATOM	1636	CB	HIS	A	213	26.626	49.370	−1.770	1.00	76.11	C
ATOM	1637	CG	HIS	A	213	25.940	48.762	−0.583	1.00	80.49	C
ATOM	1638	ND1	HIS	A	213	24.793	49.248	−0.089	1.00	85.45	N
ATOM	1639	CD2	HIS	A	213	26.269	47.663	0.196	1.00	76.28	C
ATOM	1640	CE1	HIS	A	213	24.414	48.508	0.966	1.00	78.97	C
ATOM	1641	NE2	HIS	A	213	25.320	47.542	1.139	1.00	80.59	N
ATOM	1642	N	ALA	A	214	27.809	46.791	−3.129	1.00	81.48	N
ATOM	1643	CA	ALA	A	214	28.210	45.403	−2.990	1.00	74.53	C
ATOM	1644	C	ALA	A	214	28.201	44.993	−1.521	1.00	78.64	C
ATOM	1645	O	ALA	A	214	28.235	45.840	−0.641	1.00	81.11	O
ATOM	1646	CB	ALA	A	214	29.576	45.198	−3.602	1.00	73.03	C
ATOM	1647	N	GLU	A	215	28.132	43.698	−1.241	1.00	84.45	N
ATOM	1648	CA	GLU	A	215	28.042	43.279	0.149	1.00	83.99	C
ATOM	1649	C	GLU	A	215	29.357	43.526	0.882	1.00	82.89	C
ATOM	1650	O	GLU	A	215	30.441	43.389	0.308	1.00	87.85	O
ATOM	1651	CB	GLU	A	215	27.603	41.834	0.260	1.00	86.85	C
ATOM	1652	CG	GLU	A	215	26.580	41.640	1.367	1.00	110.26	C
ATOM	1653	CD	GLU	A	215	26.453	40.188	1.800	1.00	124.02	C
ATOM	1654	OE1	GLU	A	215	26.139	39.947	2.991	1.00	117.32	O
ATOM	1655	OE2	GLU	A	215	26.682	39.288	0.955	1.00	130.15	O
ATOM	1656	N	TYR	A	216	29.255	43.932	2.140	1.00	76.50	N
ATOM	1657	CA	TYR	A	216	30.431	44.288	2.917	1.00	72.59	C
ATOM	1658	C	TYR	A	216	30.143	44.086	4.376	1.00	68.58	C
ATOM	1659	O	TYR	A	216	28.992	44.062	4.775	1.00	67.75	O
ATOM	1660	CB	TYR	A	216	30.825	45.759	2.690	1.00	78.90	C
ATOM	1661	CG	TYR	A	216	29.886	46.781	3.341	1.00	77.86	C
ATOM	1662	CD1	TYR	A	216	29.967	47.065	4.708	1.00	75.78	C
ATOM	1663	CD2	TYR	A	216	28.933	47.468	2.583	1.00	73.30	C
ATOM	1664	CE1	TYR	A	216	29.118	47.980	5.304	1.00	75.06	C
ATOM	1665	CE2	TYR	A	216	28.079	48.393	3.169	1.00	72.90	C
ATOM	1666	CZ	TYR	A	216	28.175	48.643	4.533	1.00	77.30	C
ATOM	1667	OH	TYR	A	216	27.327	49.556	5.137	1.00	74.00	O
ATOM	1668	N	THR	A	217	31.206	44.005	5.169	1.00	71.36	N
ATOM	1669	CA	THR	A	217	31.114	43.756	6.596	1.00	74.84	C
ATOM	1670	C	THR	A	217	32.256	44.458	7.276	1.00	75.33	C
ATOM	1671	O	THR	A	217	33.399	44.404	6.811	1.00	84.27	O
ATOM	1672	CB	THR	A	217	31.247	42.255	6.933	1.00	76.03	C
ATOM	1673	OG1	THR	A	217	30.233	41.521	6.248	1.00	82.07	O
ATOM	1674	CG2	THR	A	217	31.087	42.023	8.417	1.00	73.41	C
ATOM	1675	N	LEU	A	218	31.940	45.102	8.387	1.00	72.31	N
ATOM	1676	CA	LEU	A	218	32.960	45.672	9.237	1.00	76.23	C
ATOM	1677	C	LEU	A	218	33.058	44.843	10.494	1.00	81.64	C
ATOM	1678	O	LEU	A	218	32.044	44.505	11.090	1.00	91.00	O
ATOM	1679	CB	LEU	A	218	32.629	47.123	9.564	1.00	67.31	C
ATOM	1680	CG	LEU	A	218	32.495	47.961	8.297	1.00	65.78	C
ATOM	1681	CD1	LEU	A	218	32.045	49.364	8.654	1.00	70.98	C
ATOM	1682	CD2	LEU	A	218	33.818	47.989	7.532	1.00	67.36	C
ATOM	1683	N	GLU	A	219	34.282	44.515	10.891	1.00	85.84	N
ATOM	1684	CA	GLU	A	219	34.505	43.572	11.967	1.00	80.16	C
ATOM	1685	C	GLU	A	219	35.474	44.086	12.990	1.00	85.71	C
ATOM	1686	O	GLU	A	219	36.393	44.844	12.672	1.00	95.14	O
ATOM	1687	CB	GLU	A	219	35.055	42.268	11.410	1.00	79.55	C
ATOM	1688	CG	GLU	A	219	34.114	41.539	10.473	1.00	81.66	C
ATOM	1689	CD	GLU	A	219	34.699	40.233	9.983	1.00	89.09	C
ATOM	1690	OE1	GLU	A	219	35.555	39.652	10.698	1.00	86.41	O
ATOM	1691	OE2	GLU	A	219	34.293	39.788	8.885	1.00	91.38	O
ATOM	1692	N	ARG	A	220	35.274	43.651	14.227	1.00	91.74	N
ATOM	1693	CA	ARG	A	220	36.263	43.856	15.263	1.00	95.98	C
ATOM	1694	C	ARG	A	220	37.223	42.666	15.202	1.00	94.65	C
ATOM	1695	O	ARG	A	220	36.787	41.523	15.067	1.00	101.89	O
ATOM	1696	CB	ARG	A	220	35.588	43.973	16.627	1.00	100.86	C
ATOM	1697	CG	ARG	A	220	36.074	45.164	17.431	1.00	111.47	C
ATOM	1698	CD	ARG	A	220	35.676	45.045	18.889	1.00	125.97	C
ATOM	1699	NE	ARG	A	220	36.821	45.319	19.753	1.00	139.80	N
ATOM	1700	CZ	ARG	A	220	37.738	44.415	20.105	1.00	151.82	C
ATOM	1701	NH1	ARG	A	220	37.657	43.158	19.678	1.00	150.89	N
ATOM	1702	NH2	ARG	A	220	38.745	44.769	20.894	1.00	156.60	N
ATOM	1703	N	GLY	A	221	38.525	42.931	15.251	1.00	88.77	N
ATOM	1704	CA	GLY	A	221	39.508	41.858	15.159	1.00	83.01	C
ATOM	1705	C	GLY	A	221	40.921	42.348	14.954	1.00	86.58	C
ATOM	1706	O	GLY	A	221	41.136	43.505	14.604	1.00	87.88	O
ATOM	1707	N	ASP	A	222	41.884	41.465	15.209	1.00	89.53	N
ATOM	1708	CA	ASP	A	222	43.289	41.717	14.906	1.00	83.58	C
ATOM	1709	C	ASP	A	222	43.596	40.874	13.690	1.00	91.87	C
ATOM	1710	O	ASP	A	222	43.194	39.707	13.626	1.00	98.81	O
ATOM	1711	CB	ASP	A	222	44.182	41.311	16.072	1.00	79.28	C
ATOM	1712	CG	ASP	A	222	45.624	41.777	15.906	1.00	87.66	C
ATOM	1713	OD1	ASP	A	222	46.226	41.542	14.834	1.00	89.79	O
ATOM	1714	OD2	ASP	A	222	46.174	42.373	16.864	1.00	91.36	O
ATOM	1715	N	PHE	A	223	44.283	41.458	12.710	1.00	91.82	N
ATOM	1716	CA	PHE	A	223	44.526	40.731	11.467	1.00	85.01	C
ATOM	1717	C	PHE	A	223	45.759	39.814	11.532	1.00	84.32	C
ATOM	1718	O	PHE	A	223	46.111	39.131	10.571	1.00	92.47	O
ATOM	1719	CB	PHE	A	223	44.506	41.660	10.240	1.00	78.39	C
ATOM	1720	CG	PHE	A	223	45.510	42.769	10.276	1.00	74.44	C
ATOM	1721	CD1	PHE	A	223	46.882	42.504	10.211	1.00	78.35	C
ATOM	1722	CD2	PHE	A	223	45.086	44.084	10.312	1.00	73.69	C
ATOM	1723	CE1	PHE	A	223	47.809	43.538	10.222	1.00	72.35	C
ATOM	1724	CE2	PHE	A	223	46.002	45.128	10.321	1.00	74.59	C
ATOM	1725	CZ	PHE	A	223	47.366	44.857	10.279	1.00	73.76	C
ATOM	1726	N	LEU	A	224	46.398	39.801	12.689	1.00	82.96	N
ATOM	1727	CA	LEU	A	224	47.440	38.834	12.972	1.00	86.73	C
ATOM	1728	C	LEU	A	224	46.870	37.647	13.760	1.00	88.46	C
ATOM	1729	O	LEU	A	224	47.506	36.603	13.837	1.00	88.87	O
ATOM	1730	CB	LEU	A	224	48.605	39.506	13.708	1.00	78.66	C
ATOM	1731	CG	LEU	A	224	49.084	40.808	13.049	1.00	75.02	C
ATOM	1732	CD1	LEU	A	224	50.067	41.570	13.927	1.00	67.80	C
ATOM	1733	CD2	LEU	A	224	49.688	40.517	11.679	1.00	74.77	C
ATOM	1734	N	SER	A	225	45.661	37.803	14.309	1.00	92.27	N
ATOM	1735	CA	SER	A	225	44.995	36.735	15.065	1.00	95.35	C
ATOM	1736	C	SER	A	225	44.915	35.460	14.245	1.00	103.93	C
ATOM	1737	O	SER	A	225	44.696	35.505	13.031	1.00	108.59	O
ATOM	1738	CB	SER	A	225	43.587	37.140	15.495	1.00	90.35	C
ATOM	1739	OG	SER	A	225	42.655	36.879	14.460	1.00	96.73	O
ATOM	1740	N	GLU	A	226	45.079	34.330	14.928	1.00	112.30	N
ATOM	1741	CA	GLU	A	226	45.109	33.012	14.298	1.00	107.86	C
ATOM	1742	C	GLU	A	226	44.072	32.866	13.186	1.00	103.68	C
ATOM	1743	O	GLU	A	226	44.403	32.449	12.075	1.00	101.39	O
ATOM	1744	CB	GLU	A	226	44.927	31.915	15.359	1.00	110.45	C
ATOM	1745	CG	GLU	A	226	45.447	30.544	14.942	1.00	107.60	C
ATOM	1746	CD	GLU	A	226	46.897	30.588	14.476	1.00	112.49	C
ATOM	1747	OE1	GLU	A	226	47.234	29.876	13.499	1.00	110.29	O
ATOM	1748	OE2	GLU	A	226	47.698	31.347	15.073	1.00	105.39	O
ATOM	1749	N	GLU	A	227	42.833	33.243	13.493	1.00	102.88	N
ATOM	1750	CA	GLU	A	227	41.721	33.171	12.551	1.00	105.95	C
ATOM	1751	C	GLU	A	227	42.018	33.862	11.218	1.00	108.94	C
ATOM	1752	O	GLU	A	227	41.635	33.361	10.152	1.00	108.40	O
ATOM	1753	CB	GLU	A	227	40.470	33.783	13.178	1.00	111.01	C
ATOM	1754	CG	GLU	A	227	39.167	33.307	12.547	1.00	116.65	C
ATOM	1755	CD	GLU	A	227	38.115	34.405	12.454	1.00	120.83	C
ATOM	1756	OE1	GLU	A	227	38.033	35.247	13.376	1.00	115.49	O
ATOM	1757	OE2	GLU	A	227	37.366	34.433	11.451	1.00	116.37	O
ATOM	1758	N	TRP	A	228	42.709	35.001	11.279	1.00	100.39	N
ATOM	1759	CA	TRP	A	228	42.984	35.784	10.080	1.00	96.82	C
ATOM	1760	C	TRP	A	228	43.972	35.183	9.122	1.00	100.77	C
ATOM	1761	O	TRP	A	228	43.929	35.500	7.925	1.00	103.75	O
ATOM	1762	CB	TRP	A	228	43.292	37.241	10.421	1.00	98.86	C
ATOM	1763	CG	TRP	A	228	42.000	38.008	10.507	1.00	99.38	C
ATOM	1764	CD1	TRP	A	228	41.259	38.309	11.648	1.00	98.45	C
ATOM	1765	CD2	TRP	A	228	41.193	38.512	9.388	1.00	97.28	C
ATOM	1766	NE1	TRP	A	228	40.098	38.968	11.320	1.00	95.93	N
ATOM	1767	CE2	TRP	A	228	39.997	39.126	9.986	1.00	94.92	C
ATOM	1768	CE3	TRP	A	228	41.345	38.536	8.005	1.00	90.35	C
ATOM	1769	CZ2	TRP	A	228	39.023	39.734	9.216	1.00	89.84	C
ATOM	1770	CZ3	TRP	A	228	40.349	39.146	7.238	1.00	89.51	C
ATOM	1771	CH2	TRP	A	228	39.214	39.726	7.832	1.00	92.12	C
ATOM	1772	N	ARG	A	229	44.848	34.306	9.615	1.00	92.23	N
ATOM	1773	CA	ARG	A	229	45.781	33.590	8.740	1.00	90.74	C
ATOM	1774	C	ARG	A	229	45.028	32.974	7.574	1.00	90.55	C
ATOM	1775	O	ARG	A	229	45.372	33.183	6.412	1.00	87.29	O
ATOM	1776	CB	ARG	A	229	46.513	32.470	9.482	1.00	95.77	C
ATOM	1777	CG	ARG	A	229	47.408	32.903	10.626	1.00	99.63	C
ATOM	1778	CD	ARG	A	229	48.472	31.858	10.920	1.00	94.73	C
ATOM	1779	NE	ARG	A	229	49.456	32.361	11.881	1.00	99.55	N
ATOM	1780	CZ	ARG	A	229	50.683	32.773	11.564	1.00	100.25	C
ATOM	1781	NH1	ARG	A	229	51.093	32.727	10.295	1.00	98.38	N
ATOM	1782	NH2	ARG	A	229	51.503	33.226	12.518	1.00	89.44	N
ATOM	1783	N	GLU	A	230	43.987	32.214	7.891	1.00	101.10	N
ATOM	1784	CA	GLU	A	230	43.221	31.527	6.862	1.00	105.37	C
ATOM	1785	C	GLU	A	230	42.596	32.544	5.895	1.00	103.20	C
ATOM	1786	O	GLU	A	230	42.808	32.474	4.676	1.00	91.76	O
ATOM	1787	CB	GLU	A	230	42.172	30.610	7.511	1.00	115.36	C
ATOM	1788	CG	GLU	A	230	41.288	29.833	6.537	1.00	134.43	C
ATOM	1789	CD	GLU	A	230	42.061	29.187	5.396	1.00	149.04	C
ATOM	1790	OE1	GLU	A	230	42.999	28.401	5.667	1.00	162.60	O
ATOM	1791	OE2	GLU	A	230	41.724	29.465	4.223	1.00	151.39	O
ATOM	1792	N	ARG	A	231	41.869	33.506	6.466	1.00	98.29	N
ATOM	1793	CA	ARG	A	231	41.124	34.511	5.706	1.00	87.49	C
ATOM	1794	C	ARG	A	231	42.003	35.267	4.725	1.00	85.14	C
ATOM	1795	O	ARG	A	231	41.687	35.342	3.530	1.00	83.14	O
ATOM	1796	CB	ARG	A	231	40.421	35.458	6.663	1.00	81.13	C
ATOM	1797	CG	ARG	A	231	39.553	34.694	7.643	1.00	87.95	C
ATOM	1798	CD	ARG	A	231	38.765	35.591	8.566	1.00	84.41	C
ATOM	1799	NE	ARG	A	231	37.724	36.311	7.848	1.00	89.10	N
ATOM	1800	CZ	ARG	A	231	36.902	37.181	8.421	1.00	95.85	C
ATOM	1801	NH1	ARG	A	231	35.984	37.796	7.695	1.00	94.79	N
ATOM	1802	NH2	ARG	A	231	37.000	37.438	9.722	1.00	98.43	N
ATOM	1803	N	ILE	A	232	43.122	35.796	5.221	1.00	76.17	N
ATOM	1804	CA	ILE	A	232	44.094	36.465	4.353	1.00	74.31	C
ATOM	1805	C	ILE	A	232	44.519	35.614	3.144	1.00	77.97	C
ATOM	1806	O	ILE	A	232	44.642	36.119	2.014	1.00	77.48	O
ATOM	1807	CB	ILE	A	232	45.356	36.856	5.120	1.00	65.87	C
ATOM	1808	CG1	ILE	A	232	45.083	38.082	5.988	1.00	70.21	C
ATOM	1809	CG2	ILE	A	232	46.495	37.088	4.137	1.00	62.82	C
ATOM	1810	CD1	ILE	A	232	46.268	38.583	6.797	1.00	73.21	C
ATOM	1811	N	ALA	A	233	44.753	34.329	3.396	1.00	76.27	N
ATOM	1812	CA	ALA	A	233	45.180	33.427	2.356	1.00	78.91	C
ATOM	1813	C	ALA	A	233	44.069	33.336	1.325	1.00	82.57	C
ATOM	1814	O	ALA	A	233	44.329	33.245	0.112	1.00	80.07	O
ATOM	1815	CB	ALA	A	233	45.503	32.071	2.949	1.00	83.76	C
ATOM	1816	N	ASN	A	234	42.833	33.423	1.814	1.00	82.31	N
ATOM	1817	CA	ASN	A	234	41.664	33.408	0.942	1.00	93.16	C
ATOM	1818	C	ASN	A	234	41.291	34.711	0.233	1.00	95.55	C
ATOM	1819	O	ASN	A	234	40.514	34.688	−0.725	1.00	95.59	O
ATOM	1820	CB	ASN	A	234	40.446	32.864	1.682	1.00	102.99	C
ATOM	1821	CG	ASN	A	234	39.945	31.579	1.074	1.00	112.30	C
ATOM	1822	OD1	ASN	A	234	38.871	31.546	0.471	1.00	114.54	O
ATOM	1823	ND2	ASN	A	234	40.742	30.516	1.190	1.00	115.09	N
ATOM	1824	N	THR	A	235	41.824	35.841	0.693	1.00	85.97	N
ATOM	1825	CA	THR	A	235	41.472	37.118	0.091	1.00	80.68	C
ATOM	1826	C	THR	A	235	42.267	37.349	−1.188	1.00	76.85	C
ATOM	1827	O	THR	A	235	43.464	37.079	−1.200	1.00	84.40	O
ATOM	1828	CB	THR	A	235	41.718	38.262	1.080	1.00	84.75	C
ATOM	1829	OG1	THR	A	235	40.953	38.030	2.273	1.00	87.00	O
ATOM	1830	CG2	THR	A	235	41.319	39.593	0.461	1.00	82.34	C
ATOM	1831	N	SER	A	236	41.607	37.836	−2.248	1.00	69.34	N
ATOM	1832	CA	SER	A	236	42.277	38.166	−3.535	1.00	62.74	C
ATOM	1833	C	SER	A	236	42.670	39.610	−3.695	1.00	69.52	C
ATOM	1834	O	SER	A	236	43.537	39.904	−4.500	1.00	78.65	O
ATOM	1835	CB	SER	A	236	41.419	37.803	−4.747	1.00	65.24	C
ATOM	1836	OG	SER	A	236	40.140	38.425	−4.729	1.00	63.39	O
ATOM	1837	N	VAL	A	237	42.005	40.524	−2.981	1.00	74.37	N
ATOM	1838	CA	VAL	A	237	42.435	41.926	−3.001	1.00	72.39	C
ATOM	1839	C	VAL	A	237	42.599	42.519	−1.607	1.00	71.71	C
ATOM	1840	O	VAL	A	237	41.633	42.630	−0.853	1.00	72.83	O
ATOM	1841	CB	VAL	A	237	41.508	42.832	−3.821	1.00	69.05	C
ATOM	1842	CG1	VAL	A	237	42.000	44.266	−3.733	1.00	65.31	C
ATOM	1843	CG2	VAL	A	237	41.477	42.395	−5.273	1.00	68.43	C
ATOM	1844	N	ILE	A	238	43.826	42.920	−1.292	1.00	59.87	N
ATOM	1845	CA	ILE	A	238	44.144	43.423	0.013	1.00	62.06	C
ATOM	1846	C	ILE	A	238	44.604	44.851	−0.146	1.00	65.99	C
ATOM	1847	O	ILE	A	238	45.508	45.149	−0.956	1.00	64.28	O
ATOM	1848	CB	ILE	A	238	45.338	42.674	0.664	1.00	70.91	C
ATOM	1849	CG1	ILE	A	238	45.200	41.144	0.574	1.00	67.92	C
ATOM	1850	CG2	ILE	A	238	45.569	43.180	2.094	1.00	66.60	C
ATOM	1851	CD1	ILE	A	238	44.536	40.501	1.765	1.00	66.86	C
ATOM	1852	N	PHE	A	239	44.009	45.731	0.647	1.00	60.98	N
ATOM	1853	CA	PHE	A	239	44.499	47.089	0.742	1.00	64.21	C
ATOM	1854	C	PHE	A	239	45.021	47.209	2.156	1.00	66.93	C
ATOM	1855	O	PHE	A	239	44.313	46.835	3.116	1.00	69.94	O
ATOM	1856	CB	PHE	A	239	43.363	48.095	0.534	1.00	66.27	C
ATOM	1857	CG	PHE	A	239	43.062	48.433	−0.903	1.00	62.56	C
ATOM	1858	CD1	PHE	A	239	43.556	47.685	−1.948	1.00	62.93	C
ATOM	1859	CD2	PHE	A	239	42.243	49.523	−1.199	1.00	65.85	C
ATOM	1860	CE1	PHE	A	239	43.256	48.018	−3.261	1.00	65.90	C
ATOM	1861	CE2	PHE	A	239	41.938	49.859	−2.504	1.00	60.25	C
ATOM	1862	CZ	PHE	A	239	42.443	49.106	−3.539	1.00	62.56	C
ATOM	1863	N	VAL	A	240	46.246	47.714	2.286	1.00	59.96	N
ATOM	1864	CA	VAL	A	240	46.854	47.908	3.588	1.00	60.72	C
ATOM	1865	C	VAL	A	240	47.709	49.158	3.562	1.00	65.75	C
ATOM	1866	O	VAL	A	240	48.636	49.289	2.750	1.00	68.65	O
ATOM	1867	CB	VAL	A	240	47.678	46.672	4.041	1.00	68.66	C
ATOM	1868	CG1	VAL	A	240	48.798	46.336	3.050	1.00	66.92	C
ATOM	1869	CG2	VAL	A	240	48.248	46.874	5.441	1.00	71.13	C
ATOM	1870	N	ASN	A	241	47.370	50.091	4.437	1.00	65.21	N
ATOM	1871	CA	ASN	A	241	48.103	51.322	4.515	1.00	73.76	C
ATOM	1872	C	ASN	A	241	49.145	51.152	5.575	1.00	77.63	C
ATOM	1873	O	ASN	A	241	48.932	51.503	6.737	1.00	82.65	O
ATOM	1874	CB	ASN	A	241	47.182	52.481	4.865	1.00	79.15	C
ATOM	1875	CG	ASN	A	241	47.893	53.819	4.817	1.00	76.98	C
ATOM	1876	OD1	ASN	A	241	49.095	53.907	4.537	1.00	78.09	O
ATOM	1877	ND2	ASN	A	241	47.154	54.868	5.091	1.00	75.81	N
ATOM	1878	N	ASN	A	242	50.273	50.595	5.167	1.00	80.92	N
ATOM	1879	CA	ASN	A	242	51.285	50.154	6.112	1.00	83.82	C
ATOM	1880	C	ASN	A	242	52.369	51.182	6.397	1.00	91.28	C
ATOM	1881	O	ASN	A	242	53.425	50.837	6.921	1.00	97.75	O
ATOM	1882	CB	ASN	A	242	51.917	48.869	5.601	1.00	79.06	C
ATOM	1883	CG	ASN	A	242	52.501	49.018	4.209	1.00	82.85	C
ATOM	1884	OD1	ASN	A	242	51.955	49.722	3.355	1.00	83.64	O
ATOM	1885	ND2	ASN	A	242	53.599	48.326	3.963	1.00	79.84	N
ATOM	1886	N	PHE	A	243	52.100	52.449	6.088	1.00	96.93	N
ATOM	1887	CA	PHE	A	243	53.166	53.449	6.060	1.00	91.16	C
ATOM	1888	C	PHE	A	243	53.981	53.497	7.331	1.00	84.26	C
ATOM	1889	O	PHE	A	243	55.167	53.771	7.287	1.00	97.41	O
ATOM	1890	CB	PHE	A	243	52.648	54.851	5.735	1.00	100.61	C
ATOM	1891	CG	PHE	A	243	53.698	55.739	5.123	1.00	112.53	C
ATOM	1892	CD1	PHE	A	243	53.944	55.706	3.748	1.00	116.76	C
ATOM	1893	CD2	PHE	A	243	54.467	56.586	5.916	1.00	116.64	C
ATOM	1894	CE1	PHE	A	243	54.923	56.506	3.175	1.00	112.49	C
ATOM	1895	CE2	PHE	A	243	55.446	57.392	5.346	1.00	122.36	C
ATOM	1896	CZ	PHE	A	243	55.674	57.352	3.975	1.00	121.65	C
ATOM	1897	N	ALA	A	244	53.340	53.231	8.458	1.00	84.23	N
ATOM	1898	CA	ALA	A	244	53.988	53.358	9.752	1.00	81.19	C
ATOM	1899	C	ALA	A	244	53.910	52.034	10.498	1.00	86.84	C
ATOM	1900	O	ALA	A	244	53.786	52.002	11.719	1.00	91.27	O
ATOM	1901	CB	ALA	A	244	53.333	54.472	10.565	1.00	76.22	C
ATOM	1902	N	PHE	A	245	53.980	50.933	9.768	1.00	82.29	N
ATOM	1903	CA	PHE	A	245	53.969	49.644	10.419	1.00	81.54	C
ATOM	1904	C	PHE	A	245	55.315	49.223	11.017	1.00	92.59	C
ATOM	1905	O	PHE	A	245	55.369	48.598	12.091	1.00	96.05	O
ATOM	1906	CB	PHE	A	245	53.459	48.598	9.460	1.00	77.62	C
ATOM	1907	CG	PHE	A	245	51.977	48.496	9.444	1.00	77.21	C
ATOM	1908	CD1	PHE	A	245	51.224	49.126	10.425	1.00	73.56	C
ATOM	1909	CD2	PHE	A	245	51.329	47.732	8.485	1.00	75.18	C
ATOM	1910	CE1	PHE	A	245	49.849	49.016	10.441	1.00	66.30	C
ATOM	1911	CE2	PHE	A	245	49.954	47.612	8.497	1.00	72.44	C
ATOM	1912	CZ	PHE	A	245	49.215	48.251	9.480	1.00	70.19	C
ATOM	1913	N	GLY	A	246	56.397	49.553	10.323	1.00	88.31	N
ATOM	1914	CA	GLY	A	246	57.720	49.148	10.769	1.00	104.15	C
ATOM	1915	C	GLY	A	246	58.009	47.650	10.702	1.00	114.88	C
ATOM	1916	O	GLY	A	246	57.209	46.864	10.184	1.00	117.90	O
ATOM	1917	N	PRO	A	247	59.155	47.242	11.263	1.00	119.54	N
ATOM	1918	CA	PRO	A	247	59.771	45.922	11.083	1.00	110.66	C
ATOM	1919	C	PRO	A	247	58.935	44.706	11.557	1.00	104.35	C
ATOM	1920	O	PRO	A	247	58.721	43.758	10.795	1.00	93.41	O
ATOM	1921	CB	PRO	A	247	61.064	46.048	11.892	1.00	121.22	C
ATOM	1922	CG	PRO	A	247	60.761	47.082	12.935	1.00	120.00	C
ATOM	1923	CD	PRO	A	247	59.906	48.075	12.223	1.00	116.71	C
ATOM	1924	N	GLU	A	248	58.483	44.737	12.804	1.00	104.43	N
ATOM	1925	CA	GLU	A	248	57.789	43.610	13.406	1.00	101.94	C
ATOM	1926	C	GLU	A	248	56.602	43.187	12.547	1.00	102.25	C
ATOM	1927	O	GLU	A	248	56.507	42.027	12.132	1.00	104.07	O
ATOM	1928	CB	GLU	A	248	57.351	43.981	14.834	1.00	116.76	C
ATOM	1929	CG	GLU	A	248	56.506	42.945	15.565	1.00	128.47	C
ATOM	1930	CD	GLU	A	248	57.289	41.715	15.991	1.00	134.27	C
ATOM	1931	OE1	GLU	A	248	57.667	41.637	17.184	1.00	148.32	O
ATOM	1932	OE2	GLU	A	248	57.525	40.826	15.140	1.00	116.67	O
ATOM	1933	N	VAL	A	249	55.721	44.141	12.246	1.00	101.69	N
ATOM	1934	CA	VAL	A	249	54.461	43.821	11.570	1.00	90.03	C
ATOM	1935	C	VAL	A	249	54.629	43.524	10.072	1.00	87.59	C
ATOM	1936	O	VAL	A	249	53.930	42.651	9.533	1.00	81.23	O
ATOM	1937	CB	VAL	A	249	53.361	44.871	11.824	1.00	90.91	C
ATOM	1938	CG1	VAL	A	249	52.001	44.271	11.514	1.00	88.95	C
ATOM	1939	CG2	VAL	A	249	53.387	45.338	13.275	1.00	94.02	C
ATOM	1940	N	ASP	A	250	55.556	44.214	9.399	1.00	80.30	N
ATOM	1941	CA	ASP	A	250	55.762	43.921	7.980	1.00	92.01	C
ATOM	1942	C	ASP	A	250	56.070	42.442	7.824	1.00	90.39	C
ATOM	1943	O	ASP	A	250	55.456	41.765	6.997	1.00	91.57	O
ATOM	1944	CB	ASP	A	250	56.820	44.821	7.311	1.00	100.33	C
ATOM	1945	CG	ASP	A	250	56.221	46.145	6.718	1.00	115.15	C
ATOM	1946	OD1	ASP	A	250	54.983	46.294	6.515	1.00	100.86	O
ATOM	1947	OD2	ASP	A	250	57.021	47.064	6.440	1.00	127.45	O
ATOM	1948	N	HIS	A	251	56.965	41.939	8.677	1.00	92.37	N
ATOM	1949	CA	HIS	A	251	57.337	40.526	8.675	1.00	89.23	C
ATOM	1950	C	HIS	A	251	56.168	39.585	8.857	1.00	86.01	C
ATOM	1951	O	HIS	A	251	55.937	38.695	8.023	1.00	71.69	O
ATOM	1952	CB	HIS	A	251	58.417	40.220	9.713	1.00	102.40	C
ATOM	1953	CG	HIS	A	251	58.768	38.750	9.780	1.00	107.09	C
ATOM	1954	ND1	HIS	A	251	59.610	38.162	8.894	1.00	99.42	N
ATOM	1955	CD2	HIS	A	251	58.301	37.737	10.619	1.00	94.57	C
ATOM	1956	CE1	HIS	A	251	59.693	36.853	9.170	1.00	101.35	C
ATOM	1957	NE2	HIS	A	251	58.886	36.592	10.223	1.00	105.98	N
ATOM	1958	N	GLN	A	252	55.413	39.744	9.939	1.00	79.08	N
ATOM	1959	CA	GLN	A	252	54.230	38.904	10.080	1.00	85.53	C
ATOM	1960	C	GLN	A	252	53.340	38.946	8.838	1.00	86.38	C
ATOM	1961	O	GLN	A	252	52.762	37.931	8.458	1.00	88.19	O
ATOM	1962	CB	GLN	A	252	53.420	39.294	11.296	1.00	91.20	C
ATOM	1963	CG	GLN	A	252	54.018	38.846	12.606	1.00	94.95	C
ATOM	1964	CD	GLN	A	252	53.759	39.875	13.677	1.00	105.26	C
ATOM	1965	OE1	GLN	A	252	54.354	40.956	13.664	1.00	112.73	O
ATOM	1966	NE2	GLN	A	252	52.854	39.561	14.601	1.00	98.21	N
ATOM	1967	N	LEU	A	253	53.224	40.112	8.203	1.00	83.15	N
ATOM	1968	CA	LEU	A	253	52.339	40.216	7.051	1.00	82.16	C
ATOM	1969	C	LEU	A	253	52.866	39.393	5.879	1.00	85.70	C
ATOM	1970	O	LEU	A	253	52.129	38.553	5.333	1.00	83.65	O
ATOM	1971	CB	LEU	A	253	52.070	41.669	6.669	1.00	81.14	C
ATOM	1972	CG	LEU	A	253	51.089	42.423	7.584	1.00	77.64	C
ATOM	1973	CD1	LEU	A	253	51.024	43.903	7.231	1.00	70.63	C
ATOM	1974	CD2	LEU	A	253	49.701	41.813	7.560	1.00	66.81	C
ATOM	1975	N	LYS	A	254	54.139	39.613	5.528	1.00	77.46	N
ATOM	1976	CA	LYS	A	254	54.835	38.806	4.521	1.00	72.77	C
ATOM	1977	C	LYS	A	254	54.535	37.329	4.715	1.00	75.93	C
ATOM	1978	O	LYS	A	254	54.145	36.646	3.773	1.00	77.92	O
ATOM	1979	CB	LYS	A	254	56.334	39.021	4.618	1.00	73.27	C
ATOM	1980	CG	LYS	A	254	56.864	40.250	3.911	1.00	73.79	C
ATOM	1981	CD	LYS	A	254	57.926	40.918	4.759	1.00	66.02	C
ATOM	1982	CE	LYS	A	254	58.956	41.588	3.868	1.00	71.80	C
ATOM	1983	NZ	LYS	A	254	59.755	42.632	4.588	1.00	78.03	N
ATOM	1984	N	GLU	A	255	54.715	36.852	5.950	1.00	82.22	N
ATOM	1985	CA	GLU	A	255	54.346	35.490	6.363	1.00	83.05	C
ATOM	1986	C	GLU	A	255	52.959	35.155	5.806	1.00	80.41	C
ATOM	1987	O	GLU	A	255	52.839	34.311	4.924	1.00	80.58	O
ATOM	1988	CB	GLU	A	255	54.353	35.403	7.896	1.00	93.30	C
ATOM	1989	CG	GLU	A	255	54.815	34.108	8.560	1.00	96.35	C
ATOM	1990	CD	GLU	A	255	54.771	34.220	10.096	1.00	113.99	C
ATOM	1991	OE1	GLU	A	255	53.893	33.578	10.726	1.00	106.03	O
ATOM	1992	OE2	GLU	A	255	55.594	34.976	10.685	1.00	115.14	O
ATOM	1993	N	ARG	A	256	51.932	35.873	6.266	1.00	77.67	N
ATOM	1994	CA	ARG	A	256	50.548	35.588	5.898	1.00	71.97	C
ATOM	1995	C	ARG	A	256	50.222	35.750	4.409	1.00	76.40	C
ATOM	1996	O	ARG	A	256	49.360	35.036	3.884	1.00	84.88	O
ATOM	1997	CB	ARG	A	256	49.596	36.425	6.740	1.00	78.24	C
ATOM	1998	CG	ARG	A	256	49.994	36.529	8.200	1.00	77.55	C
ATOM	1999	CD	ARG	A	256	48.773	36.470	9.104	1.00	78.62	C
ATOM	2000	NE	ARG	A	256	49.067	36.438	10.545	1.00	85.56	N
ATOM	2001	CZ	ARG	A	256	50.279	36.448	11.121	1.00	87.62	C
ATOM	2002	NH1	ARG	A	256	51.414	36.485	10.418	1.00	77.74	N
ATOM	2003	NH2	ARG	A	256	50.353	36.421	12.443	1.00	86.74	N
ATOM	2004	N	PHE	A	257	50.905	36.664	3.718	1.00	73.22	N
ATOM	2005	CA	PHE	A	257	50.728	36.796	2.255	1.00	78.10	C
ATOM	2006	C	PHE	A	257	51.159	35.592	1.426	1.00	83.07	C
ATOM	2007	O	PHE	A	257	50.536	35.295	0.403	1.00	78.15	O
ATOM	2008	CB	PHE	A	257	51.451	38.025	1.708	1.00	79.16	C
ATOM	2009	CG	PHE	A	257	50.939	39.317	2.259	1.00	79.37	C
ATOM	2010	CD1	PHE	A	257	49.616	39.430	2.696	1.00	77.14	C
ATOM	2011	CD2	PHE	A	257	51.771	40.423	2.342	1.00	74.50	C
ATOM	2012	CE1	PHE	A	257	49.145	40.615	3.220	1.00	70.14	C
ATOM	2013	CE2	PHE	A	257	51.305	41.613	2.863	1.00	72.45	C
ATOM	2014	CZ	PHE	A	257	49.992	41.708	3.303	1.00	71.11	C
ATOM	2015	N	ALA	A	258	52.231	34.923	1.870	1.00	92.89	N
ATOM	2016	CA	ALA	A	258	52.832	33.773	1.172	1.00	81.33	C
ATOM	2017	C	ALA	A	258	51.848	32.643	0.886	1.00	81.73	C
ATOM	2018	O	ALA	A	258	52.020	31.897	−0.078	1.00	80.67	O
ATOM	2019	CB	ALA	A	258	54.021	33.258	1.939	1.00	76.19	C
ATOM	2020	N	ASN	A	259	50.802	32.538	1.699	1.00	78.90	N
ATOM	2021	CA	ASN	A	259	49.730	31.588	1.423	1.00	80.88	C
ATOM	2022	C	ASN	A	259	48.630	32.057	0.447	1.00	87.04	C
ATOM	2023	O	ASN	A	259	47.599	31.407	0.332	1.00	93.73	O
ATOM	2024	CB	ASN	A	259	49.101	31.146	2.738	1.00	78.57	C
ATOM	2025	CG	ASN	A	259	50.090	30.439	3.635	1.00	85.97	C
ATOM	2026	OD1	ASN	A	259	50.919	29.655	3.161	1.00	89.90	O
ATOM	2027	ND2	ASN	A	259	50.020	30.713	4.933	1.00	76.58	N
ATOM	2028	N	MET	A	260	48.817	33.165	−0.259	1.00	82.66	N
ATOM	2029	CA	MET	A	260	47.717	33.662	−1.087	1.00	83.28	C
ATOM	2030	C	MET	A	260	47.657	32.957	−2.439	1.00	77.61	C
ATOM	2031	O	MET	A	260	48.689	32.576	−2.978	1.00	77.27	O
ATOM	2032	CB	MET	A	260	47.792	35.180	−1.255	1.00	82.22	C
ATOM	2033	CG	MET	A	260	47.371	35.949	−0.007	1.00	84.81	C
ATOM	2034	SD	MET	A	260	47.742	37.707	−0.165	1.00	79.19	S
ATOM	2035	CE	MET	A	260	46.453	38.161	−1.326	1.00	79.49	C
ATOM	2036	N	LYS	A	261	46.449	32.791	−2.980	1.00	74.07	N
ATOM	2037	CA	LYS	A	261	46.267	32.136	−4.276	1.00	71.32	C
ATOM	2038	C	LYS	A	261	47.006	32.882	−5.361	1.00	70.01	C
ATOM	2039	O	LYS	A	261	47.399	34.017	−5.179	1.00	71.48	O
ATOM	2040	CB	LYS	A	261	44.793	32.032	−4.653	1.00	76.26	C
ATOM	2041	CG	LYS	A	261	43.975	31.021	−3.861	1.00	76.65	C
ATOM	2042	CD	LYS	A	261	42.777	30.595	−4.700	1.00	89.36	C
ATOM	2043	CE	LYS	A	261	41.869	29.635	−3.951	1.00	108.27	C
ATOM	2044	NZ	LYS	A	261	41.240	30.268	−2.754	1.00	108.68	N
ATOM	2045	N	GLU	A	262	47.222	32.226	−6.488	1.00	83.47	N
ATOM	2046	CA	GLU	A	262	47.913	32.842	−7.612	1.00	85.74	C
ATOM	2047	C	GLU	A	262	47.026	33.985	−8.084	1.00	84.11	C
ATOM	2048	O	GLU	A	262	45.810	33.840	−8.093	1.00	83.67	O
ATOM	2049	CB	GLU	A	262	48.109	31.793	−8.713	1.00	84.45	C
ATOM	2050	CG	GLU	A	262	48.875	32.264	−9.939	1.00	85.74	C
ATOM	2051	CD	GLU	A	262	50.374	32.239	−9.739	1.00	95.36	C
ATOM	2052	OE1	GLU	A	262	51.083	32.638	−10.694	1.00	96.16	O
ATOM	2053	OE2	GLU	A	262	50.833	31.828	−8.640	1.00	93.25	O
ATOM	2054	N	GLY	A	263	47.615	35.127	−8.432	1.00	83.08	N
ATOM	2055	CA	GLY	A	263	46.824	36.276	−8.908	1.00	83.61	C
ATOM	2056	C	GLY	A	263	46.428	37.328	−7.864	1.00	84.36	C
ATOM	2057	O	GLY	A	263	46.303	38.516	−8.192	1.00	84.95	O
ATOM	2058	N	GLY	A	264	46.218	36.891	−6.619	1.00	71.91	N
ATOM	2059	CA	GLY	A	264	45.983	37.772	−5.478	1.00	67.16	C
ATOM	2060	C	GLY	A	264	46.798	39.056	−5.476	1.00	75.62	C
ATOM	2061	O	GLY	A	264	47.974	39.076	−5.891	1.00	81.64	O
ATOM	2062	N	ARG	A	265	46.174	40.138	−5.010	1.00	73.30	N
ATOM	2063	CA	ARG	A	265	46.805	41.448	−5.063	1.00	68.43	C
ATOM	2064	C	ARG	A	265	46.910	42.115	−3.713	1.00	68.78	C
ATOM	2065	O	ARG	A	265	46.018	41.967	−2.866	1.00	67.38	O
ATOM	2066	CB	ARG	A	265	46.124	42.344	−6.084	1.00	63.05	C
ATOM	2067	CG	ARG	A	265	46.530	41.955	−7.493	1.00	68.85	C
ATOM	2068	CD	ARG	A	265	45.498	42.346	−8.531	1.00	70.35	C
ATOM	2069	NE	ARG	A	265	44.181	41.746	−8.304	1.00	69.00	N
ATOM	2070	CZ	ARG	A	265	43.086	42.100	−8.976	1.00	71.57	C
ATOM	2071	NH1	ARG	A	265	41.919	41.523	−8.708	1.00	73.68	N
ATOM	2072	NH2	ARG	A	265	43.151	43.050	−9.911	1.00	68.87	N
ATOM	2073	N	ILE	A	266	48.031	42.808	−3.511	1.00	62.17	N
ATOM	2074	CA	ILE	A	266	48.220	43.587	−2.312	1.00	67.87	C
ATOM	2075	C	ILE	A	266	48.617	44.965	−2.735	1.00	66.84	C
ATOM	2076	O	ILE	A	266	49.578	45.125	−3.488	1.00	70.97	O
ATOM	2077	CB	ILE	A	266	49.301	43.022	−1.368	1.00	73.16	C
ATOM	2078	CG1	ILE	A	266	48.930	41.615	−0.884	1.00	80.20	C
ATOM	2079	CG2	ILE	A	266	49.482	43.920	−0.153	1.00	57.48	C
ATOM	2080	CD1	ILE	A	266	49.641	40.496	−1.623	1.00	82.57	C
ATOM	2081	N	VAL	A	267	47.858	45.954	−2.260	1.00	63.56	N
ATOM	2082	CA	VAL	A	267	48.154	47.353	−2.554	1.00	63.38	C
ATOM	2083	C	VAL	A	267	48.492	48.045	−1.247	1.00	60.36	C
ATOM	2084	O	VAL	A	267	47.738	47.934	−0.266	1.00	60.44	O
ATOM	2085	CB	VAL	A	267	46.990	48.081	−3.277	1.00	63.01	C
ATOM	2086	CG1	VAL	A	267	47.518	49.333	−3.935	1.00	63.15	C
ATOM	2087	CG2	VAL	A	267	46.352	47.203	−4.347	1.00	60.18	C
ATOM	2088	N	SER	A	268	49.625	48.741	−1.225	1.00	55.69	N
ATOM	2089	CA	SER	A	268	50.149	49.271	0.035	1.00	65.22	C
ATOM	2090	C	SER	A	268	50.967	50.547	−0.172	1.00	67.01	C
ATOM	2091	O	SER	A	268	51.286	50.899	−1.311	1.00	68.27	O
ATOM	2092	CB	SER	A	268	51.032	48.215	0.722	1.00	63.06	C
ATOM	2093	OG	SER	A	268	52.241	48.000	−0.013	1.00	68.63	O
ATOM	2094	N	SER	A	269	51.338	51.203	0.926	1.00	58.34	N
ATOM	2095	CA	SER	A	269	52.183	52.371	0.843	1.00	68.44	C
ATOM	2096	C	SER	A	269	53.670	52.046	0.911	1.00	72.99	C
ATOM	2097	O	SER	A	269	54.476	52.706	0.267	1.00	79.05	O
ATOM	2098	CB	SER	A	269	51.796	53.445	1.867	1.00	68.10	C
ATOM	2099	OG	SER	A	269	51.375	52.882	3.086	1.00	79.47	O
ATOM	2100	N	LYS	A	270	54.037	51.048	1.702	1.00	83.43	N
ATOM	2101	CA	LYS	A	270	55.411	50.551	1.721	1.00	74.37	C
ATOM	2102	C	LYS	A	270	55.411	49.207	1.026	1.00	71.57	C
ATOM	2103	O	LYS	A	270	54.481	48.412	1.216	1.00	72.40	O
ATOM	2104	CB	LYS	A	270	55.872	50.348	3.144	1.00	77.09	C
ATOM	2105	CG	LYS	A	270	56.210	51.589	3.942	1.00	88.61	C
ATOM	2106	CD	LYS	A	270	56.145	51.165	5.401	1.00	100.62	C
ATOM	2107	CE	LYS	A	270	57.248	51.730	6.277	1.00	99.29	C
ATOM	2108	NZ	LYS	A	270	57.169	51.054	7.608	1.00	95.61	N
ATOM	2109	N	PRO	A	271	56.452	48.925	0.227	1.00	74.05	N
ATOM	2110	CA	PRO	A	271	56.487	47.657	−0.526	1.00	73.03	C
ATOM	2111	C	PRO	A	271	56.926	46.477	0.332	1.00	71.55	C
ATOM	2112	O	PRO	A	271	57.813	46.623	1.176	1.00	76.37	O
ATOM	2113	CB	PRO	A	271	57.510	47.933	−1.622	1.00	66.95	C
ATOM	2114	CG	PRO	A	271	58.383	49.005	−1.087	1.00	61.72	C
ATOM	2115	CD	PRO	A	271	57.678	49.713	0.037	1.00	70.25	C
ATOM	2116	N	PHE	A	272	56.286	45.331	0.126	1.00	74.60	N
ATOM	2117	CA	PHE	A	272	56.579	44.101	0.884	1.00	79.36	C
ATOM	2118	C	PHE	A	272	57.683	43.236	0.267	1.00	78.78	C
ATOM	2119	O	PHE	A	272	58.247	42.374	0.940	1.00	88.26	O
ATOM	2120	CB	PHE	A	272	55.313	43.266	1.065	1.00	75.80	C
ATOM	2121	CG	PHE	A	272	54.323	43.869	2.016	1.00	72.99	C
ATOM	2122	CD1	PHE	A	272	54.587	43.913	3.385	1.00	77.12	C
ATOM	2123	CD2	PHE	A	272	53.123	44.381	1.549	1.00	67.95	C
ATOM	2124	CE1	PHE	A	272	53.668	44.461	4.273	1.00	76.42	C
ATOM	2125	CE2	PHE	A	272	52.205	44.934	2.426	1.00	72.57	C
ATOM	2126	CZ	PHE	A	272	52.475	44.974	3.790	1.00	76.37	C
ATOM	2127	N	ALA	A	273	57.946	43.452	−1.017	1.00	72.38	N
ATOM	2128	CA	ALA	A	273	59.139	42.972	−1.693	1.00	77.08	C
ATOM	2129	C	ALA	A	273	59.902	44.207	−2.165	1.00	86.24	C
ATOM	2130	O	ALA	A	273	59.525	45.320	−1.806	1.00	94.43	O
ATOM	2131	CB	ALA	A	273	58.748	42.113	−2.877	1.00	75.37	C
ATOM	2132	N	PRO	A	274	61.009	44.029	−2.917	1.00	87.28	N
ATOM	2133	CA	PRO	A	274	61.476	45.192	−3.671	1.00	83.11	C
ATOM	2134	C	PRO	A	274	61.212	45.054	−5.172	1.00	86.23	C
ATOM	2135	O	PRO	A	274	60.788	43.992	−5.655	1.00	81.75	O
ATOM	2136	CB	PRO	A	274	62.984	45.246	−3.360	1.00	83.48	C
ATOM	2137	CG	PRO	A	274	63.263	44.092	−2.438	1.00	80.53	C
ATOM	2138	CD	PRO	A	274	62.127	43.125	−2.615	1.00	81.08	C
ATOM	2139	N	LEU	A	275	61.460	46.138	−5.896	1.00	92.68	N
ATOM	2140	CA	LEU	A	275	60.977	46.294	−7.265	1.00	96.21	C
ATOM	2141	C	LEU	A	275	62.109	45.889	−8.165	1.00	104.05	C
ATOM	2142	O	LEU	A	275	61.927	45.252	−9.207	1.00	111.38	O
ATOM	2143	CB	LEU	A	275	60.604	47.766	−7.518	1.00	102.16	C
ATOM	2144	CG	LEU	A	275	60.146	48.676	−6.355	1.00	99.00	C
ATOM	2145	CD1	LEU	A	275	61.299	49.288	−5.554	1.00	97.37	C
ATOM	2146	CD2	LEU	A	275	59.260	49.776	−6.899	1.00	95.05	C
ATOM	2147	N	ASN	A	276	63.291	46.282	−7.713	1.00	116.62	N
ATOM	2148	CA	ASN	A	276	64.572	45.917	−8.264	1.00	118.47	C
ATOM	2149	C	ASN	A	276	64.965	44.545	−7.734	1.00	122.85	C
ATOM	2150	O	ASN	A	276	66.014	44.406	−7.105	1.00	132.56	O
ATOM	2151	CB	ASN	A	276	65.582	46.945	−7.762	1.00	122.86	C
ATOM	2152	CG	ASN	A	276	65.536	47.117	−6.238	1.00	126.43	C
ATOM	2153	OD1	ASN	A	276	66.498	46.777	−5.548	1.00	124.54	O
ATOM	2154	ND2	ASN	A	276	64.413	47.629	−5.708	1.00	118.18	N
ATOM	2155	N	PHE	A	277	64.124	43.536	−7.953	1.00	119.24	N
ATOM	2156	CA	PHE	A	277	64.356	42.228	−7.336	1.00	116.43	C
ATOM	2157	C	PHE	A	277	64.536	41.181	−8.400	1.00	120.15	C
ATOM	2158	O	PHE	A	277	63.625	40.916	−9.189	1.00	128.01	O
ATOM	2159	CB	PHE	A	277	63.204	41.840	−6.399	1.00	111.79	C
ATOM	2160	CG	PHE	A	277	63.403	40.527	−5.676	1.00	103.66	C
ATOM	2161	CD1	PHE	A	277	63.943	40.496	−4.386	1.00	101.29	C
ATOM	2162	CD2	PHE	A	277	63.018	39.319	−6.266	1.00	99.39	C
ATOM	2163	CE1	PHE	A	277	64.111	39.291	−3.707	1.00	100.57	C
ATOM	2164	CE2	PHE	A	277	63.193	38.109	−5.598	1.00	96.91	C
ATOM	2165	CZ	PHE	A	277	63.736	38.094	−4.317	1.00	97.30	C
ATOM	2166	N	ARG	A	278	65.728	40.601	−8.426	1.00	124.56	N
ATOM	2167	CA	ARG	A	278	66.004	39.477	−9.307	1.00	126.70	C
ATOM	2168	C	ARG	A	278	66.438	38.290	−8.452	1.00	121.84	C
ATOM	2169	O	ARG	A	278	67.041	38.453	−7.392	1.00	121.55	O
ATOM	2170	CB	ARG	A	278	67.029	39.845	−10.385	1.00	126.73	C
ATOM	2171	CG	ARG	A	278	66.548	39.521	−11.796	1.00	131.90	C
ATOM	2172	CD	ARG	A	278	67.402	40.194	−12.857	1.00	133.10	C
ATOM	2173	NE	ARG	A	278	68.738	39.604	−12.941	1.00	137.61	N
ATOM	2174	CZ	ARG	A	278	69.754	40.125	−13.624	1.00	141.09	C
ATOM	2175	NH1	ARG	A	278	69.605	41.264	−14.294	1.00	140.17	N
ATOM	2176	NH2	ARG	A	278	70.928	39.507	−13.633	1.00	137.68	N
ATOM	2177	N	ILE	A	279	66.114	37.096	−8.923	1.00	122.33	N
ATOM	2178	CA	ILE	A	279	66.071	35.906	−8.075	1.00	125.51	C
ATOM	2179	C	ILE	A	279	67.389	35.089	−8.063	1.00	130.87	C
ATOM	2180	O	ILE	A	279	67.877	34.668	−9.117	1.00	125.28	O
ATOM	2181	CB	ILE	A	279	64.806	35.076	−8.449	1.00	125.87	C
ATOM	2182	CG1	ILE	A	279	64.662	33.819	−7.582	1.00	113.99	C
ATOM	2183	CG2	ILE	A	279	64.726	34.812	−9.962	1.00	118.73	C
ATOM	2184	CD1	ILE	A	279	63.357	33.092	−7.826	1.00	119.42	C
ATOM	2185	N	ASN	A	280	67.959	34.883	−6.870	1.00	130.24	N
ATOM	2186	CA	ASN	A	280	69.268	34.211	−6.721	1.00	126.71	C
ATOM	2187	C	ASN	A	280	69.393	33.238	−5.535	1.00	126.97	C
ATOM	2188	O	ASN	A	280	68.535	33.194	−4.649	1.00	128.92	O
ATOM	2189	CB	ASN	A	280	70.413	35.245	−6.681	1.00	112.90	C
ATOM	2190	CG	ASN	A	280	70.547	35.937	−5.323	1.00	115.54	C
ATOM	2191	OD1	ASN	A	280	70.438	35.307	−4.255	1.00	106.95	O
ATOM	2192	ND2	ASN	A	280	70.807	37.244	−5.359	1.00	106.51	N
ATOM	2193	N	SER	A	281	70.496	32.492	−5.527	1.00	129.43	N
ATOM	2194	CA	SER	A	281	70.835	31.512	−4.487	1.00	127.94	C
ATOM	2195	C	SER	A	281	70.382	31.806	−3.042	1.00	127.16	C
ATOM	2196	O	SER	A	281	69.821	30.922	−2.389	1.00	122.92	O
ATOM	2197	CB	SER	A	281	72.342	31.227	−4.513	1.00	129.67	C
ATOM	2198	OG	SER	A	281	73.087	32.434	−4.453	1.00	126.91	O
ATOM	2199	N	ARG	A	282	70.620	33.024	−2.541	1.00	123.28	N
ATOM	2200	CA	ARG	A	282	70.362	33.317	−1.112	1.00	123.24	C
ATOM	2201	C	ARG	A	282	69.130	34.167	−0.798	1.00	119.87	C
ATOM	2202	O	ARG	A	282	68.884	34.498	0.367	1.00	118.62	O
ATOM	2203	CB	ARG	A	282	71.590	33.929	−0.431	1.00	127.68	C
ATOM	2204	CG	ARG	A	282	72.734	32.955	−0.182	1.00	143.60	C
ATOM	2205	CD	ARG	A	282	74.036	33.669	0.180	1.00	140.72	C
ATOM	2206	NE	ARG	A	282	74.082	35.072	−0.259	1.00	148.97	N
ATOM	2207	CZ	ARG	A	282	74.155	35.496	−1.525	1.00	145.20	C
ATOM	2208	NH1	ARG	A	282	74.171	34.638	−2.541	1.00	145.19	N
ATOM	2209	NH2	ARG	A	282	74.191	36.797	−1.779	1.00	135.62	N
ATOM	2210	N	ASN	A	283	68.366	34.526	−1.825	1.00	113.36	N
ATOM	2211	CA	ASN	A	283	67.107	35.243	−1.628	1.00	106.59	C
ATOM	2212	C	ASN	A	283	65.901	34.310	−1.804	1.00	110.16	C
ATOM	2213	O	ASN	A	283	64.756	34.752	−1.859	1.00	108.80	O
ATOM	2214	CB	ASN	A	283	67.024	36.450	−2.578	1.00	98.10	C
ATOM	2215	CG	ASN	A	283	66.939	36.051	−4.052	1.00	103.94	C
ATOM	2216	OD1	ASN	A	283	66.666	34.895	−4.403	1.00	100.67	O
ATOM	2217	ND2	ASN	A	283	67.158	37.024	−4.925	1.00	100.07	N
ATOM	2218	N	LEU	A	284	66.184	33.014	−1.871	1.00	112.50	N
ATOM	2219	CA	LEU	A	284	65.244	31.997	−2.347	1.00	107.73	C
ATOM	2220	C	LEU	A	284	63.928	31.796	−1.561	1.00	98.27	C
ATOM	2221	O	LEU	A	284	62.955	31.268	−2.100	1.00	93.09	O
ATOM	2222	CB	LEU	A	284	65.984	30.668	−2.471	1.00	114.87	C
ATOM	2223	CG	LEU	A	284	65.512	29.777	−3.612	1.00	126.71	C
ATOM	2224	CD1	LEU	A	284	65.723	30.473	−4.950	1.00	128.74	C
ATOM	2225	CD2	LEU	A	284	66.249	28.452	−3.564	1.00	126.73	C
ATOM	2226	N	SER	A	285	63.907	32.181	−0.294	1.00	87.21	N
ATOM	2227	CA	SER	A	285	62.689	32.099	0.497	1.00	96.03	C
ATOM	2228	C	SER	A	285	62.064	33.487	0.712	1.00	107.07	C
ATOM	2229	O	SER	A	285	61.034	33.610	1.385	1.00	103.89	O
ATOM	2230	CB	SER	A	285	62.999	31.471	1.846	1.00	98.40	C
ATOM	2231	OG	SER	A	285	63.978	32.240	2.527	1.00	91.85	O
ATOM	2232	N	ASP	A	286	62.713	34.521	0.165	1.00	109.54	N
ATOM	2233	CA	ASP	A	286	62.175	35.880	0.147	1.00	105.53	C
ATOM	2234	C	ASP	A	286	60.906	35.878	−0.673	1.00	107.48	C
ATOM	2235	O	ASP	A	286	60.879	35.336	−1.803	1.00	91.71	O
ATOM	2236	CB	ASP	A	286	63.147	36.874	−0.497	1.00	111.23	C
ATOM	2237	CG	ASP	A	286	64.406	37.087	0.317	1.00	120.12	C
ATOM	2238	OD1	ASP	A	286	64.413	36.758	1.522	1.00	123.58	O
ATOM	2239	OD2	ASP	A	286	65.391	37.603	−0.252	1.00	127.64	O
ATOM	2240	N	ILE	A	287	59.869	36.495	−0.099	1.00	96.69	N
ATOM	2241	CA	ILE	A	287	58.562	36.635	−0.743	1.00	84.00	C
ATOM	2242	C	ILE	A	287	58.667	37.193	−2.161	1.00	76.52	C
ATOM	2243	O	ILE	A	287	57.899	36.822	−3.035	1.00	76.12	O
ATOM	2244	CB	ILE	A	287	57.641	37.497	0.117	1.00	81.83	C
ATOM	2245	CG1	ILE	A	287	56.180	37.154	−0.165	1.00	82.11	C
ATOM	2246	CG2	ILE	A	287	57.961	38.973	−0.053	1.00	82.30	C
ATOM	2247	CD1	ILE	A	287	55.287	37.435	1.028	1.00	86.82	C
ATOM	2248	N	GLY	A	288	59.668	38.039	−2.385	1.00	76.34	N
ATOM	2249	CA	GLY	A	288	59.952	38.576	−3.702	1.00	77.28	C
ATOM	2250	C	GLY	A	288	59.988	37.561	−4.823	1.00	76.68	C
ATOM	2251	O	GLY	A	288	60.073	37.923	−5.988	1.00	86.71	O
ATOM	2252	N	THR	A	289	59.935	36.286	−4.486	1.00	83.61	N
ATOM	2253	CA	THR	A	289	60.097	35.260	−5.508	1.00	95.38	C
ATOM	2254	C	THR	A	289	58.743	34.812	−6.010	1.00	94.17	C
ATOM	2255	O	THR	A	289	58.624	34.225	−7.094	1.00	95.27	O
ATOM	2256	CB	THR	A	289	60.900	34.052	−4.990	1.00	90.75	C
ATOM	2257	OG1	THR	A	289	60.328	33.597	−3.764	1.00	91.90	O
ATOM	2258	CG2	THR	A	289	62.333	34.457	−4.730	1.00	97.09	C
ATOM	2259	N	ILE	A	290	57.719	35.106	−5.221	1.00	88.58	N
ATOM	2260	CA	ILE	A	290	56.382	34.677	−5.584	1.00	86.90	C
ATOM	2261	C	ILE	A	290	55.445	35.814	−5.978	1.00	82.87	C
ATOM	2262	O	ILE	A	290	54.245	35.596	−6.167	1.00	82.60	O
ATOM	2263	CB	ILE	A	290	55.752	33.804	−4.491	1.00	85.43	C
ATOM	2264	CG1	ILE	A	290	55.751	34.514	−3.141	1.00	80.60	C
ATOM	2265	CG2	ILE	A	290	56.493	32.483	−4.408	1.00	95.57	C
ATOM	2266	CD1	ILE	A	290	54.639	34.034	−2.232	1.00	80.76	C
ATOM	2267	N	MET	A	291	55.989	37.020	−6.118	1.00	76.16	N
ATOM	2268	CA	MET	A	291	55.153	38.162	−6.471	1.00	75.58	C
ATOM	2269	C	MET	A	291	55.784	39.208	−7.368	1.00	76.19	C
ATOM	2270	O	MET	A	291	56.904	39.665	−7.096	1.00	77.68	O
ATOM	2271	CB	MET	A	291	54.629	38.847	−5.211	1.00	71.10	C
ATOM	2272	CG	MET	A	291	55.703	39.372	−4.294	1.00	67.78	C
ATOM	2273	SD	MET	A	291	55.023	40.225	−2.851	1.00	70.94	S
ATOM	2274	CE	MET	A	291	53.723	39.139	−2.266	1.00	63.88	C
ATOM	2275	N	ARG	A	292	55.046	39.599	−8.416	1.00	76.28	N
ATOM	2276	CA	ARG	A	292	55.369	40.806	−9.179	1.00	75.00	C
ATOM	2277	C	ARG	A	292	55.082	41.997	−8.267	1.00	71.17	C
ATOM	2278	O	ARG	A	292	54.171	41.951	−7.450	1.00	76.45	O
ATOM	2279	CB	ARG	A	292	54.531	40.909	−10.443	1.00	79.51	C
ATOM	2280	CG	ARG	A	292	55.024	40.083	−11.612	1.00	92.46	C
ATOM	2281	CD	ARG	A	292	54.142	40.274	−12.841	1.00	92.16	C
ATOM	2282	NE	ARG	A	292	52.947	39.424	−12.829	1.00	94.54	N
ATOM	2283	CZ	ARG	A	292	51.688	39.862	−12.959	1.00	103.49	C
ATOM	2284	NH1	ARG	A	292	51.435	41.161	−13.113	1.00	99.39	N
ATOM	2285	NH2	ARG	A	292	50.668	38.996	−12.943	1.00	96.59	N
ATOM	2286	N	VAL	A	293	55.884	43.039	−8.393	1.00	67.83	N
ATOM	2287	CA	VAL	A	293	55.706	44.278	−7.658	1.00	70.55	C
ATOM	2288	C	VAL	A	293	55.818	45.463	−8.633	1.00	76.23	C
ATOM	2289	O	VAL	A	293	56.736	45.511	−9.450	1.00	78.92	O
ATOM	2290	CB	VAL	A	293	56.765	44.375	−6.548	1.00	68.24	C
ATOM	2291	CG1	VAL	A	293	56.857	45.783	−5.971	1.00	72.25	C
ATOM	2292	CG2	VAL	A	293	56.440	43.380	−5.457	1.00	70.38	C
ATOM	2293	N	VAL	A	294	54.877	46.401	−8.597	1.00	77.94	N
ATOM	2294	CA	VAL	A	294	55.068	47.628	−9.395	1.00	77.96	C
ATOM	2295	C	VAL	A	294	54.848	48.848	−8.521	1.00	81.79	C
ATOM	2296	O	VAL	A	294	54.087	48.798	−7.549	1.00	84.11	O
ATOM	2297	CB	VAL	A	294	54.199	47.710	−10.687	1.00	69.45	C
ATOM	2298	CG1	VAL	A	294	53.537	46.389	−11.027	1.00	63.21	C
ATOM	2299	CG2	VAL	A	294	53.121	48.765	−10.555	1.00	82.95	C
ATOM	2300	N	GLU	A	295	55.533	49.937	−8.858	1.00	89.24	N
ATOM	2301	CA	GLU	A	295	55.241	51.229	−8.250	1.00	81.68	C
ATOM	2302	C	GLU	A	295	54.122	51.898	−9.033	1.00	76.96	C
ATOM	2303	O	GLU	A	295	54.233	52.096	−10.243	1.00	73.82	O
ATOM	2304	CB	GLU	A	295	56.473	52.105	−8.243	1.00	79.52	C
ATOM	2305	CG	GLU	A	295	56.359	53.300	−7.321	1.00	79.68	C
ATOM	2306	CD	GLU	A	295	57.707	53.928	−7.015	1.00	84.18	C
ATOM	2307	OE1	GLU	A	295	58.674	53.744	−7.793	1.00	86.03	O
ATOM	2308	OE2	GLU	A	295	57.805	54.612	−5.985	1.00	89.42	O
ATOM	2309	N	LEU	A	296	53.028	52.205	−8.343	1.00	77.19	N
ATOM	2310	CA	LEU	A	296	51.929	52.946	−8.945	1.00	71.24	C
ATOM	2311	C	LEU	A	296	52.228	54.436	−8.946	1.00	77.84	C
ATOM	2312	O	LEU	A	296	52.836	54.983	−7.998	1.00	75.09	O
ATOM	2313	CB	LEU	A	296	50.636	52.696	−8.206	1.00	59.82	C
ATOM	2314	CG	LEU	A	296	50.244	51.225	−8.231	1.00	65.06	C
ATOM	2315	CD1	LEU	A	296	49.269	50.898	−7.116	1.00	65.94	C
ATOM	2316	CD2	LEU	A	296	49.687	50.754	−9.569	1.00	61.75	C
ATOM	2317	N	SER	A	297	51.787	55.072	−10.031	1.00	80.32	N
ATOM	2318	CA	SER	A	297	51.848	56.509	−10.197	1.00	73.23	C
ATOM	2319	C	SER	A	297	51.019	57.169	−9.093	1.00	75.78	C
ATOM	2320	O	SER	A	297	49.864	56.785	−8.837	1.00	76.09	O
ATOM	2321	CB	SER	A	297	51.304	56.892	−11.573	1.00	76.30	C
ATOM	2322	OG	SER	A	297	52.000	56.242	−12.635	1.00	82.54	O
ATOM	2323	N	PRO	A	298	51.615	58.147	−8.410	1.00	68.91	N
ATOM	2324	CA	PRO	A	298	50.902	58.942	−7.422	1.00	72.69	C
ATOM	2325	C	PRO	A	298	49.941	59.948	−8.087	1.00	78.50	C
ATOM	2326	O	PRO	A	298	50.028	60.193	−9.303	1.00	82.69	O
ATOM	2327	CB	PRO	A	298	52.028	59.722	−6.763	1.00	78.86	C
ATOM	2328	CG	PRO	A	298	53.003	59.946	−7.883	1.00	74.51	C
ATOM	2329	CD	PRO	A	298	52.948	58.693	−8.720	1.00	67.08	C
ATOM	2330	N	LEU	A	299	49.048	60.540	−7.301	1.00	78.63	N
ATOM	2331	CA	LEU	A	299	48.249	61.667	−7.781	1.00	78.34	C
ATOM	2332	C	LEU	A	299	49.013	62.975	−7.598	1.00	83.46	C
ATOM	2333	O	LEU	A	299	49.596	63.191	−6.526	1.00	95.24	O
ATOM	2334	CB	LEU	A	299	46.946	61.738	−7.004	1.00	75.43	C
ATOM	2335	CG	LEU	A	299	45.670	61.189	−7.620	1.00	74.16	C
ATOM	2336	CD1	LEU	A	299	44.551	61.474	−6.628	1.00	72.23	C
ATOM	2337	CD2	LEU	A	299	45.397	61.866	−8.955	1.00	71.49	C
ATOM	2338	N	LYS	A	300	49.015	63.849	−8.611	1.00	84.11	N
ATOM	2339	CA	LYS	A	300	49.678	65.170	−8.476	1.00	91.37	C
ATOM	2340	C	LYS	A	300	49.272	65.950	−7.219	1.00	99.03	C
ATOM	2341	O	LYS	A	300	50.114	66.580	−6.563	1.00	97.10	O
ATOM	2342	CB	LYS	A	300	49.490	66.035	−9.718	1.00	90.47	C
ATOM	2343	CG	LYS	A	300	50.777	66.246	−10.505	1.00	106.46	C
ATOM	2344	CD	LYS	A	300	51.471	67.566	−10.181	1.00	101.75	C
ATOM	2345	CE	LYS	A	300	52.738	67.729	−11.004	1.00	95.35	C
ATOM	2346	NZ	LYS	A	300	53.031	69.172	−11.216	1.00	102.17	N
ATOM	2347	N	GLY	A	301	47.991	65.884	−6.870	1.00	100.53	N
ATOM	2348	CA	GLY	A	301	47.514	66.522	−5.649	1.00	119.44	C
ATOM	2349	C	GLY	A	301	47.510	65.611	−4.441	1.00	125.52	C
ATOM	2350	O	GLY	A	301	46.543	65.612	−3.675	1.00	135.41	O
ATOM	2351	N	SER	A	302	48.588	64.840	−4.272	1.00	123.02	N
ATOM	2352	CA	SER	A	302	48.723	63.885	−3.164	1.00	121.56	C
ATOM	2353	C	SER	A	302	48.752	64.603	−1.819	1.00	131.11	C
ATOM	2354	O	SER	A	302	49.364	65.669	−1.703	1.00	140.60	O
ATOM	2355	CB	SER	A	302	50.010	63.072	−3.316	1.00	113.11	C
ATOM	2356	OG	SER	A	302	51.155	63.862	−3.006	1.00	108.08	O
ATOM	2357	N	VAL	A	303	48.100	64.015	−0.811	1.00	137.77	N
ATOM	2358	CA	VAL	A	303	48.179	64.503	0.579	1.00	144.45	C
ATOM	2359	C	VAL	A	303	49.659	64.729	0.937	1.00	152.42	C
ATOM	2360	O	VAL	A	303	49.984	65.595	1.754	1.00	163.65	O
ATOM	2361	CB	VAL	A	303	47.479	63.541	1.588	1.00	141.04	C
ATOM	2362	CG1	VAL	A	303	47.569	64.066	3.022	1.00	132.21	C
ATOM	2363	CG2	VAL	A	303	46.020	63.299	1.199	1.00	127.02	C
ATOM	2364	N	SER	A	304	50.534	63.947	0.294	1.00	155.40	N
ATOM	2365	CA	SER	A	304	51.995	64.109	0.324	1.00	155.10	C
ATOM	2366	C	SER	A	304	52.584	63.995	1.737	1.00	170.59	C
ATOM	2367	O	SER	A	304	53.143	64.964	2.268	1.00	183.96	O
ATOM	2368	CB	SER	A	304	52.398	65.426	−0.353	1.00	148.14	C
ATOM	2369	OG	SER	A	304	53.627	65.295	−1.036	1.00	148.61	O
ATOM	2370	N	TRP	A	305	52.461	62.804	2.330	1.00	168.67	N
ATOM	2371	CA	TRP	A	305	52.866	62.563	3.721	1.00	168.54	C
ATOM	2372	C	TRP	A	305	54.329	62.835	3.903	1.00	170.55	C
ATOM	2373	O	TRP	A	305	55.113	62.662	2.965	1.00	172.15	O
ATOM	2374	CB	TRP	A	305	52.538	61.131	4.146	1.00	178.71	C
ATOM	2375	CG	TRP	A	305	51.909	61.038	5.522	1.00	191.21	C
ATOM	2376	CD1	TRP	A	305	50.562	60.825	5.827	1.00	192.74	C
ATOM	2377	CD2	TRP	A	305	52.579	61.166	6.836	1.00	192.86	C
ATOM	2378	NE1	TRP	A	305	50.362	60.807	7.186	1.00	196.91	N
ATOM	2379	CE2	TRP	A	305	51.527	61.006	7.850	1.00	198.98	C
ATOM	2380	CE3	TRP	A	305	53.893	61.381	7.256	1.00	179.82	C
ATOM	2381	CZ2	TRP	A	305	51.803	61.067	9.214	1.00	193.12	C
ATOM	2382	CZ3	TRP	A	305	54.157	61.444	8.632	1.00	171.12	C
ATOM	2383	CH2	TRP	A	305	53.137	61.289	9.585	1.00	181.41	C
ATOM	2384	N	THR	A	306	54.700	63.257	5.116	1.00	164.44	N
ATOM	2385	CA	THR	A	306	56.075	63.662	5.482	1.00	153.53	C
ATOM	2386	C	THR	A	306	56.593	64.851	4.655	1.00	152.44	C
ATOM	2387	O	THR	A	306	57.778	64.922	4.314	1.00	146.98	O
ATOM	2388	CB	THR	A	306	57.089	62.466	5.571	1.00	151.56	C
ATOM	2389	OG1	THR	A	306	58.413	62.966	5.786	1.00	160.90	O
ATOM	2390	CG2	THR	A	306	57.108	61.579	4.318	1.00	142.50	C
ATOM	2391	N	GLY	A	307	55.684	65.788	4.365	1.00	149.27	N
ATOM	2392	CA	GLY	A	307	55.970	66.977	3.551	1.00	153.87	C
ATOM	2393	C	GLY	A	307	56.757	66.657	2.292	1.00	158.97	C
ATOM	2394	O	GLY	A	307	57.705	67.364	1.938	1.00	160.20	O
ATOM	2395	N	LYS	A	308	56.350	65.590	1.611	1.00	160.14	N
ATOM	2396	CA	LYS	A	308	57.165	64.959	0.577	1.00	159.00	C
ATOM	2397	C	LYS	A	308	56.270	64.045	−0.284	1.00	152.38	C
ATOM	2398	O	LYS	A	308	55.399	63.354	0.258	1.00	141.53	O
ATOM	2399	CB	LYS	A	308	58.298	64.167	1.259	1.00	142.65	C
ATOM	2400	CG	LYS	A	308	59.445	63.705	0.375	1.00	134.77	C
ATOM	2401	CD	LYS	A	308	59.258	62.275	−0.119	1.00	126.20	C
ATOM	2402	CE	LYS	A	308	58.904	61.309	1.003	1.00	123.04	C
ATOM	2403	NZ	LYS	A	308	59.777	61.461	2.200	1.00	114.87	N
ATOM	2404	N	PRO	A	309	56.451	64.071	−1.628	1.00	147.37	N
ATOM	2405	CA	PRO	A	309	55.661	63.178	−2.499	1.00	141.37	C
ATOM	2406	C	PRO	A	309	55.954	61.687	−2.255	1.00	141.82	C
ATOM	2407	O	PRO	A	309	57.120	61.278	−2.201	1.00	144.06	O
ATOM	2408	CB	PRO	A	309	56.070	63.607	−3.917	1.00	125.34	C
ATOM	2409	CG	PRO	A	309	56.595	64.998	−3.759	1.00	135.55	C
ATOM	2410	CD	PRO	A	309	57.262	65.023	−2.413	1.00	138.97	C
ATOM	2411	N	VAL	A	310	54.896	60.896	−2.085	1.00	130.69	N
ATOM	2412	CA	VAL	A	310	55.022	59.464	−1.791	1.00	131.06	C
ATOM	2413	C	VAL	A	310	54.166	58.667	−2.782	1.00	126.43	C
ATOM	2414	O	VAL	A	310	53.081	59.120	−3.165	1.00	124.65	O
ATOM	2415	CB	VAL	A	310	54.651	59.156	−0.304	1.00	138.87	C
ATOM	2416	CG1	VAL	A	310	54.094	57.744	−0.118	1.00	132.34	C
ATOM	2417	CG2	VAL	A	310	55.849	59.388	0.619	1.00	132.03	C
ATOM	2418	N	SER	A	311	54.658	57.499	−3.208	1.00	111.56	N
ATOM	2419	CA	SER	A	311	53.870	56.613	−4.079	1.00	104.58	C
ATOM	2420	C	SER	A	311	53.520	55.278	−3.413	1.00	88.55	C
ATOM	2421	O	SER	A	311	53.717	55.108	−2.210	1.00	83.20	O
ATOM	2422	CB	SER	A	311	54.541	56.396	−5.435	1.00	106.30	C
ATOM	2423	OG	SER	A	311	55.504	55.373	−5.336	1.00	107.88	O
ATOM	2424	N	TYR	A	312	52.974	54.354	−4.201	1.00	79.26	N
ATOM	2425	CA	TYR	A	312	52.304	53.165	−3.668	1.00	79.08	C
ATOM	2426	C	TYR	A	312	52.586	51.981	−4.563	1.00	76.54	C
ATOM	2427	O	TYR	A	312	53.082	52.150	−5.685	1.00	68.58	O
ATOM	2428	CB	TYR	A	312	50.781	53.390	−3.566	1.00	80.09	C
ATOM	2429	CG	TYR	A	312	50.463	54.753	−3.056	1.00	85.43	C
ATOM	2430	CD1	TYR	A	312	50.473	55.018	−1.685	1.00	94.54	C
ATOM	2431	CD2	TYR	A	312	50.221	55.809	−3.943	1.00	93.43	C
ATOM	2432	CE1	TYR	A	312	50.224	56.294	−1.206	1.00	102.27	C
ATOM	2433	CE2	TYR	A	312	49.979	57.090	−3.475	1.00	93.42	C
ATOM	2434	CZ	TYR	A	312	49.981	57.321	−2.110	1.00	100.39	C
ATOM	2435	OH	TYR	A	312	49.736	58.583	−1.639	1.00	119.09	O
ATOM	2436	N	TYR	A	313	52.225	50.792	−4.078	1.00	72.47	N
ATOM	2437	CA	TYR	A	313	52.769	49.562	−4.616	1.00	62.45	C
ATOM	2438	C	TYR	A	313	51.744	48.470	−4.791	1.00	65.28	C
ATOM	2439	O	TYR	A	313	50.982	48.129	−3.875	1.00	73.20	O
ATOM	2440	CB	TYR	A	313	53.911	49.091	−3.737	1.00	58.83	C
ATOM	2441	CG	TYR	A	313	55.006	50.127	−3.569	1.00	64.33	C
ATOM	2442	CD1	TYR	A	313	55.982	50.292	−4.537	1.00	67.83	C
ATOM	2443	CD2	TYR	A	313	55.057	50.939	−2.441	1.00	64.55	C
ATOM	2444	CE1	TYR	A	313	56.980	51.242	−4.389	1.00	72.85	C
ATOM	2445	CE2	TYR	A	313	56.049	51.882	−2.282	1.00	67.15	C
ATOM	2446	CZ	TYR	A	313	57.005	52.034	−3.259	1.00	72.31	C
ATOM	2447	OH	TYR	A	313	58.001	52.976	−3.108	1.00	76.67	O
ATOM	2448	N	LEU	A	314	51.725	47.931	−5.998	1.00	61.90	N
ATOM	2449	CA	LEU	A	314	50.870	46.811	−6.319	1.00	67.08	C
ATOM	2450	C	LEU	A	314	51.709	45.529	−6.383	1.00	72.17	C
ATOM	2451	O	LEU	A	314	52.651	45.419	−7.190	1.00	72.07	O
ATOM	2452	CB	LEU	A	314	50.156	47.071	−7.653	1.00	59.23	C
ATOM	2453	CG	LEU	A	314	49.479	45.876	−8.337	1.00	62.96	C
ATOM	2454	CD1	LEU	A	314	48.302	45.278	−7.553	1.00	55.90	C
ATOM	2455	CD2	LEU	A	314	49.091	46.254	−9.765	1.00	56.83	C
ATOM	2456	N	HIS	A	315	51.371	44.574	−5.523	1.00	71.77	N
ATOM	2457	CA	HIS	A	315	52.008	43.266	−5.553	1.00	69.03	C
ATOM	2458	C	HIS	A	315	51.008	42.267	−6.017	1.00	67.34	C
ATOM	2459	O	HIS	A	315	49.905	42.171	−5.481	1.00	71.85	O
ATOM	2460	CB	HIS	A	315	52.532	42.819	−4.184	1.00	69.91	C
ATOM	2461	CG	HIS	A	315	53.069	43.929	−3.295	1.00	70.86	C
ATOM	2462	ND1	HIS	A	315	52.272	44.829	−2.695	1.00	75.74	N
ATOM	2463	CD2	HIS	A	315	54.356	44.188	−2.840	1.00	72.03	C
ATOM	2464	CE1	HIS	A	315	53.014	45.649	−1.925	1.00	75.47	C
ATOM	2465	NE2	HIS	A	315	54.287	45.260	−2.017	1.00	77.00	N
ATOM	2466	N	THR	A	316	51.388	41.497	−7.017	1.00	70.99	N
ATOM	2467	CA	THR	A	316	50.546	40.418	−7.506	1.00	75.93	C
ATOM	2468	C	THR	A	316	51.250	39.081	−7.238	1.00	80.12	C
ATOM	2469	O	THR	A	316	52.397	38.870	−7.669	1.00	72.92	O
ATOM	2470	CB	THR	A	316	50.268	40.594	−9.016	1.00	73.68	C
ATOM	2471	OG1	THR	A	316	49.686	41.883	−9.232	1.00	78.35	O
ATOM	2472	CG2	THR	A	316	49.318	39.523	−9.537	1.00	66.60	C
ATOM	2473	N	ILE	A	317	50.568	38.197	−6.509	1.00	79.40	N
ATOM	2474	CA	ILE	A	317	51.025	36.822	−6.336	1.00	78.30	C
ATOM	2475	C	ILE	A	317	51.183	36.165	−7.712	1.00	86.07	C
ATOM	2476	O	ILE	A	317	50.194	35.883	−8.413	1.00	83.61	O
ATOM	2477	CB	ILE	A	317	50.052	35.993	−5.461	1.00	72.56	C
ATOM	2478	CG1	ILE	A	317	50.022	36.496	−4.018	1.00	69.65	C
ATOM	2479	CG2	ILE	A	317	50.440	34.525	−5.448	1.00	80.76	C
ATOM	2480	CD1	ILE	A	317	51.368	36.864	−3.426	1.00	68.78	C
ATOM	2481	N	ASP	A	318	52.439	35.948	−8.093	1.00	89.92	N
ATOM	2482	CA	ASP	A	318	52.789	35.252	−9.333	1.00	92.89	C
ATOM	2483	C	ASP	A	318	53.905	34.214	−9.089	1.00	94.09	C
ATOM	2484	O	ASP	A	318	55.102	34.566	−9.054	1.00	88.00	O
ATOM	2485	CB	ASP	A	318	53.198	36.276	−10.394	1.00	89.90	C
ATOM	2486	CG	ASP	A	318	53.631	35.640	−11.691	1.00	93.99	C
ATOM	2487	OD1	ASP	A	318	53.229	34.482	−11.966	1.00	90.26	O
ATOM	2488	OD2	ASP	A	318	54.370	36.323	−12.438	1.00	95.88	O
ATOM	2489	N	ARG	A	319	53.508	32.947	−8.906	1.00	84.46	N
ATOM	2490	CA	ARG	A	319	54.480	31.869	−8.612	1.00	89.38	C
ATOM	2491	C	ARG	A	319	55.371	31.455	−9.772	1.00	88.53	C
ATOM	2492	O	ARG	A	319	56.532	31.128	−9.566	1.00	87.53	O
ATOM	2493	CB	ARG	A	319	53.809	30.637	−8.025	1.00	83.51	C
ATOM	2494	CG	ARG	A	319	53.975	30.566	−6.529	1.00	82.51	C
ATOM	2495	CD	ARG	A	319	52.659	30.225	−5.880	1.00	78.57	C
ATOM	2496	NE	ARG	A	319	52.671	30.604	−4.475	1.00	78.70	N
ATOM	2497	CZ	ARG	A	319	51.580	30.929	−3.791	1.00	85.46	C
ATOM	2498	NH1	ARG	A	319	50.398	30.930	−4.394	1.00	86.59	N
ATOM	2499	NH2	ARG	A	319	51.663	31.256	−2.509	1.00	84.76	N
ATOM	2500	N	THR	A	320	54.831	31.473	−10.983	1.00	82.07	N
ATOM	2501	CA	THR	A	320	55.628	31.188	−12.156	1.00	83.33	C
ATOM	2502	C	THR	A	320	57.010	31.867	−12.128	1.00	90.69	C
ATOM	2503	O	THR	A	320	57.951	31.359	−12.734	1.00	95.36	O
ATOM	2504	CB	THR	A	320	54.894	31.564	−13.464	1.00	85.36	C
ATOM	2505	OG1	THR	A	320	55.018	32.978	−13.715	1.00	73.28	O
ATOM	2506	CG2	THR	A	320	53.408	31.096	−13.438	1.00	73.13	C
ATOM	2507	N	ILE	A	321	57.128	33.010	−11.444	1.00	95.96	N
ATOM	2508	CA	ILE	A	321	58.433	33.672	−11.259	1.00	94.64	C
ATOM	2509	C	ILE	A	321	59.420	32.670	−10.662	1.00	93.70	C
ATOM	2510	O	ILE	A	321	60.534	32.522	−11.160	1.00	96.07	O
ATOM	2511	CB	ILE	A	321	58.363	34.911	−10.326	1.00	93.79	C
ATOM	2512	CG1	ILE	A	321	57.452	36.004	−10.898	1.00	99.78	C
ATOM	2513	CG2	ILE	A	321	59.753	35.483	−10.064	1.00	80.61	C
ATOM	2514	CD1	ILE	A	321	57.167	37.129	−9.913	1.00	96.93	C
ATOM	2515	N	LEU	A	322	58.993	31.991	−9.596	1.00	87.70	N
ATOM	2516	CA	LEU	A	322	59.761	30.913	−8.965	1.00	85.26	C
ATOM	2517	C	LEU	A	322	59.982	29.750	−9.937	1.00	92.53	C
ATOM	2518	O	LEU	A	322	61.122	29.335	−10.178	1.00	89.44	O
ATOM	2519	CB	LEU	A	322	59.031	30.412	−7.713	1.00	74.26	C
ATOM	2520	CG	LEU	A	322	59.804	29.614	−6.662	1.00	74.13	C
ATOM	2521	CD1	LEU	A	322	61.033	30.355	−6.144	1.00	72.69	C
ATOM	2522	CD2	LEU	A	322	58.903	29.212	−5.506	1.00	67.18	C
ATOM	2523	N	GLU	A	323	58.881	29.245	−10.498	1.00	94.51	N
ATOM	2524	CA	GLU	A	323	58.914	28.176	−11.495	1.00	92.52	C
ATOM	2525	C	GLU	A	323	59.990	28.436	−12.551	1.00	93.78	C
ATOM	2526	O	GLU	A	323	60.826	27.579	−12.798	1.00	101.05	O
ATOM	2527	CB	GLU	A	323	57.525	27.954	−12.109	1.00	88.46	C
ATOM	2528	CG	GLU	A	323	56.479	27.595	−11.056	1.00	100.05	C
ATOM	2529	CD	GLU	A	323	55.053	27.480	−11.581	1.00	110.58	C
ATOM	2530	OE1	GLU	A	323	54.775	27.988	−12.691	1.00	112.02	O
ATOM	2531	OE2	GLU	A	323	54.203	26.879	−10.872	1.00	107.65	O
ATOM	2532	N	ASN	A	324	60.006	29.635	−13.121	1.00	97.99	N
ATOM	2533	CA	ASN	A	324	61.020	30.001	−14.106	1.00	103.97	C
ATOM	2534	C	ASN	A	324	62.461	29.839	−13.620	1.00	107.46	C
ATOM	2535	O	ASN	A	324	63.335	29.504	−14.414	1.00	118.90	O
ATOM	2536	CB	ASN	A	324	60.795	31.420	−14.629	1.00	109.87	C
ATOM	2537	CG	ASN	A	324	59.498	31.559	−15.408	1.00	112.74	C
ATOM	2538	OD1	ASN	A	324	58.785	30.578	−15.653	1.00	104.32	O
ATOM	2539	ND2	ASN	A	324	59.180	32.791	−15.793	1.00	119.62	N
ATOM	2540	N	TYR	A	325	62.707	30.065	−12.331	1.00	97.93	N
ATOM	2541	CA	TYR	A	325	64.052	29.894	−11.760	1.00	104.99	C
ATOM	2542	C	TYR	A	325	64.432	28.417	−11.595	1.00	110.62	C
ATOM	2543	O	TYR	A	325	65.600	28.088	−11.391	1.00	105.64	O
ATOM	2544	CB	TYR	A	325	64.150	30.622	−10.424	1.00	106.27	C
ATOM	2545	CG	TYR	A	325	65.507	30.603	−9.738	1.00	116.07	C
ATOM	2546	CD1	TYR	A	325	66.561	31.409	−10.187	1.00	119.17	C
ATOM	2547	CD2	TYR	A	325	65.722	29.818	−8.603	1.00	119.90	C
ATOM	2548	CE1	TYR	A	325	67.793	31.415	−9.537	1.00	118.89	C
ATOM	2549	CE2	TYR	A	325	66.950	29.819	−7.949	1.00	123.43	C
ATOM	2550	CZ	TYR	A	325	67.981	30.618	−8.415	1.00	124.19	C
ATOM	2551	OH	TYR	A	325	69.193	30.617	−7.755	1.00	121.24	O
ATOM	2552	N	PHE	A	326	63.433	27.540	−11.676	1.00	112.98	N
ATOM	2553	CA	PHE	A	326	63.659	26.102	−11.651	1.00	110.62	C
ATOM	2554	C	PHE	A	326	63.660	25.519	−13.061	1.00	116.54	C
ATOM	2555	O	PHE	A	326	64.229	24.457	−13.295	1.00	132.07	O
ATOM	2556	CB	PHE	A	326	62.637	25.398	−10.757	1.00	98.67	C
ATOM	2557	CG	PHE	A	326	62.946	25.501	−9.284	1.00	111.70	C
ATOM	2558	CD1	PHE	A	326	62.334	26.470	−8.489	1.00	123.02	C
ATOM	2559	CD2	PHE	A	326	63.852	24.633	−8.681	1.00	110.37	C
ATOM	2560	CE1	PHE	A	326	62.614	26.564	−7.124	1.00	110.31	C
ATOM	2561	CE2	PHE	A	326	64.135	24.727	−7.320	1.00	107.89	C
ATOM	2562	CZ	PHE	A	326	63.517	25.693	−6.540	1.00	99.82	C
ATOM	2563	N	SER	A	327	63.025	26.214	−13.998	1.00	119.38	N
ATOM	2564	CA	SER	A	327	63.168	25.888	−15.412	1.00	122.32	C
ATOM	2565	C	SER	A	327	64.544	26.329	−15.885	1.00	125.23	C
ATOM	2566	O	SER	A	327	65.127	25.709	−16.776	1.00	130.69	O
ATOM	2567	CB	SER	A	327	62.102	26.591	−16.253	1.00	120.62	C
ATOM	2568	OG	SER	A	327	60.809	26.122	−15.934	1.00	124.28	O
ATOM	2569	N	SER	A	328	65.060	27.396	−15.275	1.00	117.67	N
ATOM	2570	CA	SER	A	328	66.321	27.985	−15.708	1.00	122.09	C
ATOM	2571	C	SER	A	328	67.516	27.234	−15.136	1.00	129.01	C
ATOM	2572	O	SER	A	328	68.641	27.737	−15.148	1.00	133.36	O
ATOM	2573	CB	SER	A	328	66.394	29.468	−15.341	1.00	113.67	C
ATOM	2574	OG	SER	A	328	66.566	29.629	−13.945	1.00	120.73	O
ATOM	2575	N	LEU	A	329	67.275	26.032	−14.628	1.00	133.64	N
ATOM	2576	CA	LEU	A	329	68.369	25.184	−14.177	1.00	129.59	C
ATOM	2577	C	LEU	A	329	68.321	23.828	−14.903	1.00	128.70	C
ATOM	2578	O	LEU	A	329	68.065	22.776	−14.311	1.00	125.46	O
ATOM	2579	CB	LEU	A	329	68.413	25.104	−12.637	1.00	122.10	C
ATOM	2580	CG	LEU	A	329	68.586	26.456	−11.896	1.00	115.92	C
ATOM	2581	CD1	LEU	A	329	68.375	26.351	−10.389	1.00	109.03	C
ATOM	2582	CD2	LEU	A	329	69.929	27.120	−12.180	1.00	114.03	C
ATOM	2583	N	LYS	A	330	68.515	23.915	−16.221	1.00	134.82	N
ATOM	2584	CA	LYS	A	330	68.783	22.779	−17.108	1.00	131.88	C
ATOM	2585	C	LYS	A	330	70.109	23.024	−17.827	1.00	136.09	C
ATOM	2586	O	LYS	A	330	70.734	24.079	−17.663	1.00	126.76	O
ATOM	2587	CB	LYS	A	330	67.658	22.579	−18.137	1.00	121.64	C
ATOM	2588	CG	LYS	A	330	66.649	21.509	−17.754	1.00	124.92	C
ATOM	2589	CD	LYS	A	330	65.809	21.947	−16.563	1.00	128.51	C
ATOM	2590	CE	LYS	A	330	65.620	20.811	−15.574	1.00	120.92	C
ATOM	2591	NZ	LYS	A	330	65.346	21.322	−14.205	1.00	108.06	N
TER	2592		LYS	A	330
HETATM	2593	C2	0QK	A	501	43.267	45.305	13.198	1.00	83.36	C
HETATM	2594	C4	0QK	A	501	44.663	47.218	13.113	1.00	83.08	C
HETATM	2595	C5	0QK	A	501	45.752	46.461	13.245	1.00	81.52	C
HETATM	2596	C6	0QK	A	501	45.621	45.130	13.364	1.00	85.38	C
HETATM	2597	CBI	0QK	A	501	46.059	53.920	−1.025	1.00	71.41	C
HETATM	2598	CBH	0QK	A	501	46.534	52.809	−0.099	1.00	69.19	C
HETATM	2599	CBJ	0QK	A	501	47.867	53.233	0.529	1.00	74.95	C
HETATM	2600	CBK	0QK	A	501	46.726	51.592	−0.999	1.00	65.05	C
HETATM	2601	CBE	0QK	A	501	45.595	52.578	0.943	1.00	69.40	C
HETATM	2602	CBF	0QK	A	501	45.385	51.301	1.487	1.00	62.58	C
HETATM	2603	CBG	0QK	A	501	44.446	51.137	2.514	1.00	64.53	C
HETATM	2604	CBD	0QK	A	501	44.848	53.660	1.463	1.00	65.92	C
HETATM	2605	CBC	0QK	A	501	43.913	53.483	2.490	1.00	62.12	C
HETATM	2606	CBB	0QK	A	501	43.700	52.212	3.039	1.00	62.70	C
HETATM	2607	NAZ	0QK	A	501	42.784	51.978	4.018	1.00	58.88	N
HETATM	2608	CAY	0QK	A	501	42.641	52.830	5.059	1.00	62.60	C
HETATM	2609	OBA	0QK	A	501	43.366	53.838	5.157	1.00	60.66	O
HETATM	2610	NAX	0QK	A	501	41.662	52.535	5.982	1.00	61.84	N
HETATM	2611	CAW	0QK	A	501	41.509	53.290	7.245	1.00	57.19	C
HETATM	2612	CAV	0QK	A	501	43.004	53.502	7.636	1.00	72.05	C
HETATM	2613	CAT	0QK	A	501	43.356	53.210	9.083	1.00	82.20	C
HETATM	2614	NAS	0QK	A	501	44.380	52.162	9.356	1.00	79.95	N
HETATM	2615	CAU	0QK	A	501	45.691	52.155	8.674	1.00	80.80	C
HETATM	2616	CBM	0QK	A	501	46.400	50.805	8.939	1.00	78.40	C
HETATM	2617	CBL	0QK	A	501	46.645	53.288	9.116	1.00	66.71	C
HETATM	2618	CAR	0QK	A	501	44.642	52.265	10.805	1.00	82.82	C
HETATM	2619	CAN	0QK	A	501	43.660	51.404	11.595	1.00	86.49	C
HETATM	2620	OAO	0QK	A	501	44.209	50.082	11.555	1.00	87.99	O
HETATM	2621	CAM	0QK	A	501	43.665	51.850	13.042	1.00	83.94	C
HETATM	2622	OAQ	0QK	A	501	42.321	51.998	13.460	1.00	80.10	O
HETATM	2623	CAL	0QK	A	501	44.331	50.699	13.787	1.00	84.69	C
HETATM	2624	OAP	0QK	A	501	43.697	50.453	15.048	1.00	87.52	O
HETATM	2625	CAK	0QK	A	501	44.059	49.550	12.875	1.00	83.19	C
HETATM	2626	NAG	0QK	A	501	45.066	48.488	13.030	1.00	85.72	N
HETATM	2627	CAH	0QK	A	501	46.402	48.539	13.094	1.00	75.33	C
HETATM	2628	CAI	0QK	A	501	46.818	47.278	13.227	1.00	79.57	C
HETATM	2629	N3	0QK	A	501	43.426	46.682	13.094	1.00	80.58	N
HETATM	2630	N1	0QK	A	501	44.422	44.529	13.334	1.00	85.54	N
HETATM	2631	NAJ	0QK	A	501	46.739	44.408	13.492	1.00	87.83	N
HETATM	2632	S	SO4	A	502	20.908	47.709	2.769	1.00	147.51	S
HETATM	2633	O1	SO4	A	502	22.046	46.779	2.589	1.00	138.31	O
HETATM	2634	O2	SO4	A	502	20.394	47.632	4.158	1.00	138.37	O
HETATM	2635	O3	SO4	A	502	21.370	49.089	2.494	1.00	153.96	O
HETATM	2636	O4	SO4	A	502	19.837	47.343	1.810	1.00	146.31	O
HETATM	2637	S	SO4	A	503	25.969	49.694	−12.194	1.00	132.72	S
HETATM	2638	O1	SO4	A	503	26.217	51.050	−11.657	1.00	126.36	O
HETATM	2639	O2	SO4	A	503	24.893	49.025	−11.419	1.00	128.90	O
HETATM	2640	O3	SO4	A	503	25.555	49.841	−13.609	1.00	131.79	O
HETATM	2641	O4	SO4	A	503	27.221	48.897	−12.107	1.00	142.06	O
HETATM	2642	S	SO4	A	504	32.612	58.455	−12.636	1.00	132.38	S
HETATM	2643	O1	SO4	A	504	33.933	58.779	−13.242	1.00	126.62	O
HETATM	2644	O2	SO4	A	504	32.606	57.112	−11.998	1.00	124.19	O
HETATM	2645	O3	SO4	A	504	32.233	59.462	−11.609	1.00	129.55	O
HETATM	2646	O4	SO4	A	504	31.611	58.453	−13.723	1.00	141.87	O
HETATM	2647	O	HOH	A	601	37.950	51.247	5.661	1.00	74.64	O
HETATM	2648	O	HOH	A	602	44.972	49.662	5.632	1.00	76.63	O
HETATM	2649	O	HOH	A	603	46.338	36.042	10.941	1.00	99.98	O
HETATM	2650	O	HOH	A	604	29.538	68.837	3.073	1.00	73.72	O
HETATM	2651	O	HOH	A	605	42.475	33.970	16.341	1.00	86.94	O
HETATM	2652	O	HOH	A	606	41.258	49.594	22.130	1.00	83.68	O
HETATM	2653	O	HOH	A	607	40.197	52.386	20.536	1.00	103.60	O
HETATM	2654	O	HOH	A	608	53.740	35.223	13.209	1.00	71.42	O
HETATM	2655	O	HOH	A	609	15.616	84.733	7.777	1.00	75.14	O
HETATM	2656	O	HOH	A	610	21.592	63.491	12.419	1.00	76.55	O
CONECT	2593	2629	2630
CONECT	2594	2595	2626	2629
CONECT	2595	2594	2596	2628
CONECT	2596	2595	2630	2631
CONECT	2597	2598
CONECT	2598	2597	2599	2600	2601
CONECT	2599	2598
CONECT	2600	2598
CONECT	2601	2598	2602	2604
CONECT	2602	2601	2603
CONECT	2603	2602	2606
CONECT	2604	2601	2605
CONECT	2605	2604	2606
CONECT	2606	2603	2605	2607
CONECT	2607	2606	2608
CONECT	2608	2607	2609	2610
CONECT	2609	2608
CONECT	2610	2608	2611
CONECT	2611	2610	2612
CONECT	2612	2611	2613
CONECT	2613	2612	2614
CONECT	2614	2613	2615	2618
CONECT	2615	2614	2616	2617
CONECT	2616	2615
CONECT	2617	2615
CONECT	2618	2614	2619
CONECT	2619	2618	2620	2621
CONECT	2620	2619	2625
CONECT	2621	2619	2622	2623
CONECT	2622	2621
CONECT	2623	2621	2624	2625
CONECT	2624	2623
CONECT	2625	2620	2623	2626
CONECT	2626	2594	2625	2627
CONECT	2627	2626	2628
CONECT	2628	2595	2627
CONECT	2629	2593	2594
CONECT	2630	2593	2596
CONECT	2631	2596
CONECT	2632	2633	2634	2635	2636
CONECT	2633	2632
CONECT	2634	2632
CONECT	2635	2632
CONECT	2636	2632
CONECT	2637	2638	2639	2640	2641
CONECT	2638	2637
CONECT	2639	2637
CONECT	2640	2637
CONECT	2641	2637
CONECT	2642	2643	2644	2645	2646
CONECT	2643	2642
CONECT	2644	2642
CONECT	2645	2642
CONECT	2646	2642
MASTER		413	0	4	12	11	0	6	6	2655	1	54	33
END

TABLE S2

HEADER

CRYSTAL STRUCTURE OF DOT1L IN COMPLEX WITH EPZ005676

CRYST1

154.326 154.326 47.524 90.00 90.00 120.00 P 65

SCALE1

0.006480

0.003741

0.000000

0.00000

SCALE2

0.000000

0.007482

0.000000

0.00000

SCALE3

0.000000

0.000000

0.021042

0.00000

ATOM

1

N

LEU

A

5

−58.657

−47.525

−16.411

1.00

107.90

A

N

ATOM

2

CA

LEU

A

5

−57.497

−47.204

−17.293

1.00

108.08

A

C

ATOM

3

CB

LEU

A

5

−57.628

−45.813

−17.948

1.00

108.27

A

C

ATOM

4

CG

LEU

A

5

−57.626

−44.504

−17.143

1.00

108.68

A

C

ATOM

5

CD1

LEU

A

5

−57.194

−43.327

−18.026

1.00

108.80

A

C

ATOM

6

CD2

LEU

A

5

−58.985

−44.238

−16.493

1.00

108.71

A

C

ATOM

7

C

LEU

A

5

−56.161

−47.350

−16.564

1.00

108.02

A

C

ATOM

8

O

LEU

A

5

−55.226

−47.936

−17.121

1.00

108.38

A

O

ATOM

9

N

GLU

A

6

−56.073

−46.819

−15.335

1.00

107.60

A

N

ATOM

10

CA

GLU

A

6

−54.887

−46.998

−14.459

1.00

106.72

A

C

ATOM

11

CB

GLU

A

6

−53.760

−45.991

−14.806

1.00

106.39

A

C

ATOM

12

CG

GLU

A

6

−54.106

−44.508

−14.639

1.00

106.96

A

C

ATOM

13

CD

GLU

A

6

−52.957

−43.552

−15.029

1.00

107.90

A

C

ATOM

14

OE1

GLU

A

6

−52.841

−42.462

−14.423

1.00

107.84

A

O

ATOM

15

OE2

GLU

A

6

−52.163

−43.878

−15.940

1.00

108.07

A

O

ATOM

16

C

GLU

A

6

−55.219

−47.030

−12.937

1.00

106.08

A

C

ATOM

17

O

GLU

A

6

−56.327

−46.658

−12.534

1.00

105.79

A

O

ATOM

18

N

LEU

A

7

−54.269

−47.529

−12.128

1.00

105.29

A

N

ATOM

19

CA

LEU

A

7

−54.295

−47.456

−10.645

1.00

104.13

A

C

ATOM

20

CB

LEU

A

7

−54.318

−48.851

−10.026

1.00

103.50

A

C

ATOM

21

CG

LEU

A

7

−55.428

−49.818

−10.455

1.00

103.26

A

C

ATOM

22

CD1

LEU

A

7

−55.104

−51.250

−10.069

1.00

102.78

A

C

ATOM

23

CD2

LEU

A

7

−56.791

−49.435

−9.894

1.00

103.03

A

C

ATOM

24

C

LEU

A

7

−53.080

−46.679

−10.111

1.00

103.90

A

C

ATOM

25

O

LEU

A

7

−51.986

−46.756

−10.673

1.00

104.05

A

O

ATOM

26

N

ARG

A

8

−53.261

−45.925

−9.033

1.00

103.54

A

N

ATOM

27

CA

ARG

A

8

−52.163

−45.108

−8.497

1.00

103.16

A

C

ATOM

28

CB

ARG

A

8

−52.354

−43.619

−8.836

1.00

103.46

A

C

ATOM

29

CG

ARG

A

8

−52.250

−43.281

−10.330

1.00

104.55

A

C

ATOM

30

CD

ARG

A

8

−52.146

−41.773

−10.599

1.00

105.28

A

C

ATOM

31

NE

ARG

A

8

−53.447

−41.117

−10.706

1.00

106.37

A

N

ATOM

32

CZ

ARG

A

8

−53.611

−39.806

−10.883

1.00

107.98

A

C

ATOM

33

NH1

ARG

A

8

−52.550

−39.010

−10.983

1.00

108.55

A

N

ATOM

34

NH2

ARG

A

8

−54.834

−39.282

−10.960

1.00

107.93

A

N

ATOM

35

C

ARG

A

8

−51.981

−45.273

−6.992

1.00

102.56

A

C

ATOM

36

O

ARG

A

8

−52.945

−45.202

−6.233

1.00

102.47

A

O

ATOM

37

N

LEU

A

9

−50.740

−45.496

−6.569

1.00

101.86

A

N

ATOM

38

CA

LEU

A

9

−50.417

−45.553

−5.145

1.00

101.12

A

C

ATOM

39

CB

LEU

A

9

−49.615

−46.818

−4.802

1.00

101.02

A

C

ATOM

40

CG

LEU

A

9

−50.212

−48.219

−5.004

1.00

100.46

A

C

ATOM

41

CD1

LEU

A

9

−49.170

−49.260

−4.686

1.00

99.11

A

C

ATOM

42

CD2

LEU

A

9

−51.468

−48.471

−4.174

1.00

100.38

A

C

ATOM

43

C

LEU

A

9

−49.626

−44.323

−4.733

1.00

100.72

A

C

ATOM

44

O

LEU

A

9

−48.577

−44.044

−5.308

1.00

100.61

A

O

ATOM

45

N

LYS

A

10

−50.127

−43.602

−3.733

1.00

100.19

A

N

ATOM

46

CA

LYS

A

10

−49.424

−42.445

−3.197

1.00

99.91

A

C

ATOM

47

CB

LYS

A

10

−50.378

−41.541

−2.410

1.00

99.74

A

C

ATOM

48

CG

LYS

A

10

−51.141

−40.512

−3.256

1.00

99.34

A

C

ATOM

49

CD

LYS

A

10

−52.305

−39.876

−2.477

1.00

98.37

A

C

ATOM

50

CE

LYS

A

10

−52.951

−38.690

−3.207

1.00

97.47

A

C

ATOM

51

NZ

LYS

A

10

−52.016

−37.565

−3.479

1.00

97.14

A

N

ATOM

52

C

LYS

A

10

−48.223

−42.856

−2.340

1.00

99.93

A

C

ATOM

53

O

LYS

A

10

−48.352

−43.628

−1.395

1.00

99.60

A

O

ATOM

54

N

SER

A

11

−47.053

−42.344

−2.705

1.00

100.23

A

N

ATOM

55

CA

SER

A

11

−45.827

−42.547

−1.950

1.00

100.78

A

C

ATOM

56

CB

SER

A

11

−44.690

−41.777

−2.607

1.00

100.77

A

C

ATOM

57

OG

SER

A

11

−43.759

−41.328

−1.641

1.00

100.49

A

O

ATOM

58

C

SER

A

11

−45.962

−42.108

−0.493

1.00

101.37

A

C

ATOM

59

O

SER

A

11

−46.535

−41.054

−0.219

1.00

101.58

A

O

ATOM

60

N

PRO

A

12

−45.418

−42.908

0.449

1.00

101.88

A

N

ATOM

61

CA

PRO

A

12

−45.658

−42.616

1.862

1.00

101.98

A

C

ATOM

62

CB

PRO

A

12

−45.233

−43.902

2.579

1.00

101.85

A

C

ATOM

63

CG

PRO

A

12

−44.284

−44.564

1.655

1.00

102.01

A

C

ATOM

64

CD

PRO

A

12

−44.663

−44.162

0.262

1.00

101.99

A

C

ATOM

65

C

PRO

A

12

−44.876

−41.428

2.375

1.00

102.13

A

C

ATOM

66

O

PRO

A

12

−45.253

−40.862

3.396

1.00

102.51

A

O

ATOM

67

N

VAL

A

13

−43.808

−41.042

1.690

1.00

102.24

A

N

ATOM

68

CA

VAL

A

13

−43.108

−39.813

2.068

1.00

102.61

A

C

ATOM

69

CB

VAL

A

13

−41.600

−40.023

2.336

1.00

102.51

A

C

ATOM

70

CG1

VAL

A

13

−41.417

−41.035

3.458

1.00

102.63

A

C

ATOM

71

CG2

VAL

A

13

−40.845

−40.439

1.057

1.00

102.51

A

C

ATOM

72

C

VAL

A

13

−43.367

−38.694

1.061

1.00

103.02

A

C

ATOM

73

O

VAL

A

13

−42.636

−37.689

1.018

1.00

103.28

A

O

ATOM

74

N

GLY

A

14

−44.429

−38.875

0.274

1.00

103.22

A

N

ATOM

75

CA

GLY

A

14

−44.871

−37.883

−0.697

1.00

103.31

A

C

ATOM

76

C

GLY

A

14

−43.917

−37.747

−1.866

1.00

103.50

A

C

ATOM

77

O

GLY

A

14

−43.369

−36.669

−2.100

1.00

103.60

A

O

ATOM

78

N

ALA

A

15

−43.699

−38.847

−2.583

1.00

103.51

A

N

ATOM

79

CA

ALA

A

15

−43.015

−38.804

−3.872

1.00

103.56

A

C

ATOM

80

CB

ALA

A

15

−41.936

−39.862

−3.949

1.00

103.62

A

C

ATOM

81

C

ALA

A

15

−44.010

−38.967

−5.019

1.00

103.54

A

C

ATOM

82

O

ALA

A

15

−45.210

−39.207

−4.792

1.00

103.39

A

O

ATOM

83

N

GLU

A

16

−43.500

−38.811

−6.243

1.00

103.52

A

N

ATOM

84

CA

GLU

A

16

−44.273

−39.033

−7.462

1.00

103.54

A

C

ATOM

85

CB

GLU

A

16

−43.415

−38.795

−8.717

1.00

103.40

A

C

ATOM

86

CG

GLU

A

16

−42.944

−37.337

−8.945

1.00

102.67

A

C

ATOM

87

CD

GLU

A

16

−44.083

−36.328

−9.111

0.50

101.57

A

C

ATOM

88

OE1

GLU

A

16

−45.128

−36.658

−9.718

0.50

100.58

A

O

ATOM

89

OE2

GLU

A

16

−43.918

−35.184

−8.638

0.50

101.23

A

O

ATOM

90

C

GLU

A

16

−44.834

−40.456

−7.434

1.00

103.74

A

C

ATOM

91

O

GLU

A

16

−44.073

−41.419

−7.362

1.00

103.99

A

O

ATOM

92

N

PRO

A

17

−46.170

−40.590

−7.463

1.00

103.87

A

N

ATOM

93

CA

PRO

A

17

−46.810

−41.862

−7.141

1.00

104.23

A

C

ATOM

94

CB

PRO

A

17

−48.311

−41.516

−7.184

1.00

104.08

A

C

ATOM

95

CG

PRO

A

17

−48.362

−40.057

−7.001

1.00

103.78

A

C

ATOM

96

CD

PRO

A

17

−47.175

−39.551

−7.737

1.00

103.72

A

C

ATOM

97

C

PRO

A

17

−46.492

−43.013

−8.104

1.00

104.50

A

C

ATOM

98

O

PRO

A

17

−46.070

−42.789

−9.239

1.00

104.69

A

O

ATOM

99

N

ALA

A

18

−46.693

−44.239

−7.639

1.00

104.74

A

N

ATOM

100

CA

ALA

A

18

−46.592

−45.389

−8.510

1.00

105.09

A

C

ATOM

101

CB

ALA

A

18

−46.379

−46.660

−7.713

1.00

105.05

A

C

ATOM

102

C

ALA

A

18

−47.861

−45.478

−9.323

1.00

105.42

A

C

ATOM

103

O

ALA

A

18

−48.960

−45.580

−8.767

1.00

105.44

A

O

ATOM

104

N

VAL

A

19

−47.692

−45.434

−10.642

1.00

105.93

A

N

ATOM

105

CA

VAL

A

19

−48.802

−45.519

−11.596

1.00

106.38

A

C

ATOM

106

CB

VAL

A

19

−48.698

−44.369

−12.649

1.00

106.45

A

C

ATOM

107

CG1

VAL

A

19

−47.673

−44.686

−13.767

1.00

106.75

A

C

ATOM

108

CG2

VAL

A

19

−50.062

−44.027

−13.210

1.00

106.40

A

C

ATOM

109

C

VAL

A

19

−48.872

−46.925

−12.229

1.00

106.29

A

C

ATOM

110

O

VAL

A

19

−47.834

−47.528

−12.490

1.00

106.37

A

O

ATOM

111

N

TYR

A

20

−50.081

−47.445

−12.444

1.00

106.39

A

N

ATOM

112

CA

TYR

A

20

−50.271

−48.846

−12.859

1.00

106.96

A

C

ATOM

113

CB

TYR

A

20

−50.663

−49.714

−11.664

1.00

106.95

A

C

ATOM

114

CG

TYR

A

20

−49.515

−50.151

−10.803

1.00

107.18

A

C

ATOM

115

CD1

TYR

A

20

−48.901

−49.260

−9.928

1.00

107.84

A

C

ATOM

116

CE1

TYR

A

20

−47.842

−49.650

−9.136

1.00

107.89

A

C

ATOM

117

CZ

TYR

A

20

−47.392

−50.948

−9.203

1.00

107.87

A

C

ATOM

118

OH

TYR

A

20

−46.347

−51.330

−8.399

1.00

108.59

A

O

ATOM

119

CE2

TYR

A

20

−47.989

−51.857

−10.062

1.00

107.40

A

C

ATOM

120

CD2

TYR

A

20

−49.047

−51.454

−10.851

1.00

106.94

A

C

ATOM

121

C

TYR

A

20

−51.314

−49.060

−13.953

1.00

107.46

A

C

ATOM

122

O

TYR

A

20

−52.514

−48.900

−13.706

1.00

107.44

A

O

ATOM

123

N

PRO

A

21

−50.866

−49.456

−15.160

1.00

107.88

A

N

ATOM

124

CA

PRO

A

21

−51.771

−49.671

−16.293

1.00

108.07

A

C

ATOM

125

CB

PRO

A

21

−50.811

−49.906

−17.466

1.00

108.11

A

C

ATOM

126

CG

PRO

A

21

−49.539

−49.245

−17.053

1.00

108.28

A

C

ATOM

127

CD

PRO

A

21

−49.458

−49.530

−15.578

1.00

108.10

A

C

ATOM

128

C

PRO

A

21

−52.671

−50.882

−16.098

1.00

108.13

A

C

ATOM

129

O

PRO

A

21

−52.241

−51.873

−15.519

1.00

108.33

A

O

ATOM

130

N

TRP

A

22

−53.912

−50.788

−16.568

1.00

108.25

A

N

ATOM

131

CA

TRP

A

22

−54.856

−51.905

−16.501

1.00

108.38

A

C

ATOM

132

CB

TRP

A

22

−56.138

−51.494

−15.771

1.00

108.38

A

C

ATOM

133

CG

TRP

A

22

−57.160

−52.560

−15.753

1.00

108.61

A

C

ATOM

134

CD1

TRP

A

22

−58.068

−52.829

−16.725

1.00

109.81

A

C

ATOM

135

NE1

TRP

A

22

−58.846

−53.901

−16.370

1.00

110.82

A

N

ATOM

136

CE2

TRP

A

22

−58.439

−54.351

−15.144

1.00

110.32

A

C

ATOM

137

CD2

TRP

A

22

−57.373

−53.527

−14.726

1.00

109.66

A

C

ATOM

138

CE3

TRP

A

22

−56.770

−53.778

−13.492

1.00

110.30

A

C

ATOM

139

CZ3

TRP

A

22

−57.247

−54.832

−12.724

1.00

110.81

A

C

ATOM

140

CH2

TRP

A

22

−58.308

−55.633

−13.170

1.00

110.57

A

C

ATOM

141

CZ2

TRP

A

22

−58.919

−55.407

−14.371

1.00

110.21

A

C

ATOM

142

C

TRP

A

22

−55.169

−52.433

−17.910

1.00

108.32

A

C

ATOM

143

O

TRP

A

22

−55.374

−51.635

−18.830

1.00

108.43

A

O

ATOM

144

N

PRO

A

23

−55.214

−53.772

−18.088

1.00

108.08

A

N

ATOM

145

CA

PRO

A

23

−55.095

−54.857

−17.108

1.00

107.88

A

C

ATOM

146

CB

PRO

A

23

−55.345

−56.105

−17.946

1.00

108.00

A

C

ATOM

147

CG

PRO

A

23

−54.820

−55.731

−19.284

1.00

108.15

A

C

ATOM

148

CD

PRO

A

23

−55.259

−54.305

−19.460

1.00

108.12

A

C

ATOM

149

C

PRO

A

23

−53.717

−54.940

−16.453

1.00

107.52

A

C

ATOM

150

O

PRO

A

23

−52.742

−54.415

−16.990

1.00

107.17

A

O

ATOM

151

N

LEU

A

24

−53.661

−55.610

−15.304

1.00

107.29

A

N

ATOM

152

CA

LEU

A

24

−52.480

−55.610

−14.446

1.00

106.83

A

C

ATOM

153

CB

LEU

A

24

−52.884

−55.772

−12.986

1.00

106.48

A

C

ATOM

154

CG

LEU

A

24

−53.299

−54.521

−12.246

1.00

105.13

A

C

ATOM

155

CD1

LEU

A

24

−53.735

−54.969

−10.876

1.00

104.43

A

C

ATOM

156

CD2

LEU

A

24

−52.154

−53.526

−12.188

1.00

102.73

A

C

ATOM

157

C

LEU

A

24

−51.521

−56.721

−14.800

1.00

106.92

A

C

ATOM

158

O

LEU

A

24

−51.786

−57.886

−14.482

1.00

107.12

A

O

ATOM

159

N

PRO

A

25

−50.378

−56.366

−15.410

1.00

106.73

A

N

ATOM

160

CA

PRO

A

25

−49.449

−57.374

−15.906

1.00

106.61

A

C

ATOM

161

CB

PRO

A

25

−48.194

−56.562

−16.222

1.00

106.29

A

C

ATOM

162

CG

PRO

A

25

−48.699

−55.188

−16.462

1.00

106.41

A

C

ATOM

163

CD

PRO

A

25

−49.808

−55.012

−15.498

1.00

106.57

A

C

ATOM

164

C

PRO

A

25

−49.127

−58.464

−14.881

1.00

106.57

A

C

ATOM

165

O

PRO

A

25

−49.016

−58.195

−13.686

1.00

106.47

A

O

ATOM

166

N

VAL

A

26

−49.037

−59.695

−15.363

1.00

106.67

A

N

ATOM

167

CA

VAL

A

26

−48.342

−60.738

−14.644

1.00

106.86

A

C

ATOM

168

CB

VAL

A

26

−49.089

−62.085

−14.724

1.00

106.84

A

C

ATOM

169

CG1

VAL

A

26

−48.971

−62.703

−16.111

1.00

107.27

A

C

ATOM

170

CG2

VAL

A

26

−48.582

−63.044

−13.653

1.00

107.27

A

C

ATOM

171

C

VAL

A

26

−46.910

−60.803

−15.216

1.00

106.94

A

C

ATOM

172

O

VAL

A

26

−46.716

−60.780

−16.445

1.00

107.11

A

O

ATOM

173

N

TYR

A

27

−45.921

−60.835

−14.321

1.00

106.65

A

N

ATOM

174

CA

TYR

A

27

−44.510

−60.833

−14.699

1.00

106.35

A

C

ATOM

175

CB

TYR

A

27

−43.688

−60.075

−13.656

1.00

106.33

A

C

ATOM

176

CG

TYR

A

27

−44.146

−58.660

−13.391

1.00

106.08

A

C

ATOM

177

CD1

TYR

A

27

−43.888

−57.639

−14.305

1.00

106.87

A

C

ATOM

178

CE1

TYR

A

27

−44.302

−56.330

−14.064

1.00

106.66

A

C

ATOM

179

CZ

TYR

A

27

−44.975

−56.036

−12.889

1.00

106.46

A

C

ATOM

180

OH

TYR

A

27

−45.389

−54.746

−12.648

1.00

106.52

A

O

ATOM

181

CE2

TYR

A

27

−45.231

−57.031

−11.961

1.00

106.19

A

C

ATOM

182

CD2

TYR

A

27

−44.809

−58.333

−12.213

1.00

106.23

A

C

ATOM

183

C

TYR

A

27

−43.938

−62.256

−14.907

1.00

106.44

A

C

ATOM

184

O

TYR

A

27

−43.043

−62.462

−15.752

1.00

106.21

A

O

ATOM

185

N

ASP

A

28

−44.454

−63.221

−14.142

1.00

106.21

A

N

ATOM

186

CA

ASP

A

28

−44.076

−64.626

−14.295

1.00

106.46

A

C

ATOM

187

CB

ASP

A

28

−42.673

−64.895

−13.719

1.00

106.76

A

C

ATOM

188

CG

ASP

A

28

−42.653

−64.993

−12.190

1.00

107.44

A

C

ATOM

189

OD1

ASP

A

28

−43.368

−65.854

−11.626

1.00

106.45

A

O

ATOM

190

OD2

ASP

A

28

−41.887

−64.224

−11.560

1.00

108.33

A

O

ATOM

191

C

ASP

A

28

−45.106

−65.569

−13.687

1.00

106.35

A

C

ATOM

192

O

ASP

A

28

−46.128

−65.130

−13.178

1.00

106.57

A

O

ATOM

193

N

LYS

A

29

−44.815

−66.864

−13.732

1.00

106.41

A

N

ATOM

194

CA

LYS

A

29

−45.693

−67.903

−13.195

1.00

106.83

A

C

ATOM

195

CB

LYS

A

29

−44.962

−69.259

−13.152

1.00

107.02

A

C

ATOM

196

CG

LYS

A

29

−45.886

−70.474

−13.192

1.00

107.71

A

C

ATOM

197

CD

LYS

A

29

−45.309

−71.671

−12.438

1.00

110.58

A

C

ATOM

198

CE

LYS

A

29

−44.155

−72.365

−13.176

1.00

112.07

A

C

ATOM

199

NZ

LYS

A

29

−43.588

−73.527

−12.403

1.00

111.84

A

N

ATOM

200

C

LYS

A

29

−46.229

−67.574

−11.802

1.00

106.81

A

C

ATOM

201

O

LYS

A

29

−47.380

−67.893

−11.483

1.00

106.90

A

O

ATOM

202

N

HIS

A

30

−45.385

−66.946

−10.981

1.00

106.73

A

N

ATOM

203

CA

HIS

A

30

−45.725

−66.632

−9.588

1.00

106.45

A

C

ATOM

204

CB

HIS

A

30

−44.874

−67.465

−8.620

1.00

106.54

A

C

ATOM

205

CG

HIS

A

30

−45.012

−68.946

−8.777

1.00

106.81

A

C

ATOM

206

ND1

HIS

A

30

−46.235

−69.586

−8.804

1.00

107.56

A

N

ATOM

207

CE1

HIS

A

30

−46.044

−70.888

−8.925

1.00

107.69

A

C

ATOM

208

NE2

HIS

A

30

−44.742

−71.117

−8.960

1.00

107.78

A

N

ATOM

209

CD2

HIS

A

30

−44.074

−69.919

−8.862

1.00

106.56

A

C

ATOM

210

C

HIS

A

30

−45.512

−65.161

−9.210

1.00

105.96

A

C

ATOM

211

O

HIS

A

30

−45.114

−64.891

−8.074

1.00

106.06

A

O

ATOM

212

N

HIS

A

31

−45.765

−64.219

−10.124

1.00

105.06

A

N

ATOM

213

CA

HIS

A

31

−45.543

−62.796

−9.821

1.00

104.23

A

C

ATOM

214

CB

HIS

A

31

−44.046

−62.439

−9.915

1.00

104.69

A

C

ATOM

215

CG

HIS

A

31

−43.211

−63.019

−8.810

1.00

106.26

A

C

ATOM

216

ND1

HIS

A

31

−43.690

−63.202

−7.528

1.00

107.18

A

N

ATOM

217

CE1

HIS

A

31

−42.744

−63.731

−6.775

1.00

107.46

A

C

ATOM

218

NE2

HIS

A

31

−41.662

−63.885

−7.517

1.00

107.81

A

N

ATOM

219

CD2

HIS

A

31

−41.925

−63.441

−8.790

1.00

107.42

A

C

ATOM

220

C

HIS

A

31

−46.372

−61.782

−10.617

1.00

103.01

A

C

ATOM

221

O

HIS

A

31

−45.881

−61.202

−11.575

1.00

102.92

A

O

ATOM

222

N

ASP

A

32

−47.612

−61.546

−10.188

1.00

101.71

A

N

ATOM

223

CA

ASP

A

32

−48.466

−60.514

−10.791

1.00

100.43

A

C

ATOM

224

CB

ASP

A

32

−49.965

−60.867

−10.709

1.00

100.67

A

C

ATOM

225

CG

ASP

A

32

−50.380

−61.445

−9.361

1.00

101.55

A

C

ATOM

226

CD1

ASP

A

32

−49.615

−62.210

−8.738

1.00

102.97

A

O

ATOM

227

OD2

ASP

A

32

−51.512

−61.165

−8.930

1.00

103.43

A

O

ATOM

228

C

ASP

A

32

−48.216

−59.135

−10.215

1.00

99.26

A

C

ATOM

229

O

ASP

A

32

−47.547

−58.985

−9.204

1.00

99.24

A

O

ATOM

230

N

ALA

A

33

−48.745

−58.123

−10.886

1.00

98.03

A

N

ATOM

231

CA

ALA

A

33

−48.656

−56.759

−10.391

1.00

96.77

A

C

ATOM

232

CB

ALA

A

33

−48.639

−55.757

−11.555

1.00

96.86

A

C

ATOM

233

C

ALA

A

33

−49.803

−56.475

−9.412

1.00

95.74

A

C

ATOM

234

O

ALA

A

33

−49.682

−55.618

−8.541

1.00

95.02

A

O

ATOM

235

N

ALA

A

34

−50.903

−57.217

−9.551

1.00

94.77

A

N

ATOM

236

CA

ALA

A

34

−51.979

−57.203

−8.556

1.00

93.89

A

C

ATOM

237

CB

ALA

A

34

−53.072

−58.173

−8.927

1.00

93.91

A

C

ATOM

238

C

ALA

A

34

−51.442

−57.540

−7.177

1.00

93.24

A

C

ATOM

239

O

ALA

A

34

−51.830

−56.935

−6.188

1.00

93.12

A

O

ATOM

240

N

HIS

A

35

−50.541

−58.508

−7.108

1.00

92.60

A

N

ATOM

241

CA

HIS

A

35

−49.945

−58.845

−5.832

1.00

91.83

A

C

ATOM

242

CB

HIS

A

35

−49.566

−60.324

−5.777

1.00

91.62

A

C

ATOM

243

CG

HIS

A

35

−50.731

−61.217

−5.481

0.50

90.57

A

C

ATOM

244

ND1

HIS

A

35

−51.014

−62.346

−6.217

0.50

90.07

A

N

ATOM

245

CE1

HIS

A

35

−52.104

−62.917

−5.739

0.50

89.92

A

C

ATOM

246

NE2

HIS

A

35

−52.547

−62.192

−4.728

0.50

89.36

A

N

ATOM

247

CD2

HIS

A

35

−51.707

−61.122

−4.548

0.50

89.45

A

C

ATOM

248

C

HIS

A

35

−48.806

−57.921

−5.427

1.00

91.42

A

C

ATOM

249

O

HIS

A

35

−48.578

−57.695

−4.239

1.00

91.03

A

O

ATOM

250

N

GLU

A

36

−48.129

−57.351

−6.417

1.00

91.18

A

N

ATOM

251

CA

GLU

A

36

−47.096

−56.360

−6.154

1.00

91.26

A

C

ATOM

252

CB

GLU

A

36

−46.556

−55.772

−7.477

1.00

91.13

A

C

ATOM

253

CG

GLU

A

36

−45.581

−54.591

−7.323

1.00

90.54

A

C

ATOM

254

CD

GLU

A

36

−44.818

−54.215

−8.604

1.00

89.75

A

C

ATOM

255

OE1

GLU

A

36

−44.433

−55.096

−9.391

1.00

90.85

A

O

ATOM

256

OE2

GLU

A

36

−44.556

−53.022

−8.816

1.00

88.99

A

O

ATOM

257

C

GLU

A

36

−47.718

−55.297

−5.256

1.00

91.50

A

C

ATOM

258

O

GLU

A

36

−47.150

−54.925

−4.234

1.00

90.95

A

O

ATOM

259

N

ILE

A

37

−48.918

−54.866

−5.654

1.00

92.17

A

N

ATOM

260

CA

ILE

A

37

−49.741

−53.870

−4.971

1.00

92.35

A

C

ATOM

261

CB

ILE

A

37

−51.102

−53.709

−5.700

1.00

92.24

A

C

ATOM

262

CG1

ILE

A

37

−50.916

−53.184

−7.131

1.00

92.73

A

C

ATOM

263

CD1

ILE

A

37

−50.160

−51.890

−7.261

1.00

93.34

A

C

ATOM

264

CG2

ILE

A

37

−52.065

−52.845

−4.916

1.00

92.25

A

C

ATOM

265

C

ILE

A

37

−50.023

−54.293

−3.550

1.00

92.65

A

C

ATOM

266

O

ILE

A

37

−49.499

−53.714

−2.604

1.00

92.61

A

O

ATOM

267

N

ILE

A

38

−50.846

−55.320

−3.406

1.00

93.16

A

N

ATOM

268

CA

ILE

A

38

−51.246

−55.781

−2.095

1.00

93.96

A

C

ATOM

269

CB

ILE

A

38

−52.025

−57.110

−2.184

1.00

93.95

A

C

ATOM

270

CG1

ILE

A

38

−53.388

−56.842

−2.831

1.00

93.67

A

C

ATOM

271

CD1

ILE

A

38

−54.157

−58.067

−3.249

1.00

93.99

A

C

ATOM

272

CG2

ILE

A

38

−52.219

−57.722

−0.801

1.00

94.33

A

C

ATOM

273

C

ILE

A

38

−50.068

−55.830

−1.106

1.00

94.55

A

C

ATOM

274

O

ILE

A

38

−50.228

−55.435

0.051

1.00

95.00

A

O

ATOM

275

N

GLU

A

39

−48.892

−56.264

−1.565

1.00

94.89

A

N

ATOM

276

CA

GLU

A

39

−47.697

−56.272

−0.720

1.00

95.14

A

C

ATOM

277

CB

GLU

A

39

−46.589

−57.137

−1.318

1.00

95.56

A

C

ATOM

278

CG

GLU

A

39

−46.921

−58.625

−1.454

1.00

98.10

A

C

ATOM

279

CD

GLU

A

39

−47.361

−59.267

−0.148

1.00

100.98

A

C

ATOM

280

OE1

GLU

A

39

−47.984

−60.359

−0.196

1.00

101.55

A

O

ATOM

281

OE2

GLU

A

39

−47.090

−58.676

0.924

1.00

102.90

A

O

ATOM

282

C

GLU

A

39

−47.169

−54.876

−0.482

1.00

94.82

A

C

ATOM

283

O

GLU

A

39

−46.984

−54.471

0.658

1.00

94.92

A

O

ATOM

284

N

THR

A

40

−46.930

−54.146

−1.568

1.00

95.00

A

N

ATOM

285

CA

THR

A

40

−46.428

−52.756

−1.518

1.00

94.85

A

C

ATOM

286

CB

THR

A

40

−46.570

−52.034

−2.904

1.00

94.57

A

C

ATOM

287

OG1

THR

A

40

−46.216

−52.926

−3.963

1.00

93.63

A

O

ATOM

288

CG2

THR

A

40

−45.692

−50.823

−2.988

1.00

93.55

A

C

ATOM

289

C

THR

A

40

−47.185

−51.972

−0.455

1.00

95.03

A

C

ATOM

290

O

THR

A

40

−46.605

−51.204

0.297

1.00

94.27

A

O

ATOM

291

N

ILE

A

41

−48.491

−52.195

−0.412

1.00

95.94

A

N

ATOM

292

CA

ILE

A

41

−49.348

−51.626

0.609

1.00

97.02

A

C

ATOM

293

CB

ILE

A

41

−50.852

−51.930

0.341

1.00

96.95

A

C

ATOM

294

CG1

ILE

A

41

−51.299

−51.355

−1.008

1.00

96.41

A

C

ATOM

295

CD1

ILE

A

41

−52.704

−51.772

−1.412

1.00

95.44

A

C

ATOM

296

CG2

ILE

A

41

−51.727

−51.377

1.468

1.00

97.03

A

C

ATOM

297

C

ILE

A

41

−48.934

−52.140

1.989

1.00

97.75

A

C

ATOM

298

O

ILE

A

41

−48.401

−51.379

2.798

1.00

97.80

A

O

ATOM

299

N

ARG

A

42

−49.153

−53.432

2.233

1.00

98.52

A

N

ATOM

300

CA

ARG

A

42

−48.940

−54.033

3.551

1.00

99.77

A

C

ATOM

301

CB

ARG

A

42

−49.278

−55.521

3.509

1.00

100.23

A

C

ATOM

302

CG

ARG

A

42

−50.065

−55.999

4.719

1.00

103.05

A

C

ATOM

303

CD

ARG

A

42

−50.767

−57.324

4.416

1.00

108.82

A

C

ATOM

304

NE

ARG

A

42

−51.916

−57.587

5.294

1.00

112.94

A

N

ATOM

305

CZ

ARG

A

42

−51.868

−58.243

6.461

1.00

114.85

A

C

ATOM

306

NH1

ARG

A

42

−52.993

−58.422

7.155

1.00

115.68

A

N

ATOM

307

NH2

ARG

A

42

−50.715

−58.719

6.941

1.00

114.50

A

N

ATOM

308

C

ARG

A

42

−47.532

−53.820

4.126

1.00

99.80

A

C

ATOM

309

O

ARG

A

42

−47.319

−53.932

5.340

1.00

99.70

A

O

ATOM

310

N

TRP

A

43

−46.589

−53.510

3.245

1.00

99.95

A

N

ATOM

311

CA

TRP

A

43

−45.243

−53.160

3.641

1.00

100.55

A

C

ATOM

312

CB

TRP

A

43

−44.260

−53.439

2.495

1.00

100.67

A

C

ATOM

313

CG

TRP

A

43

−43.739

−54.835

2.541

1.00

100.81

A

C

ATOM

314

CD1

TRP

A

43

−43.908

−55.813

1.604

1.00

99.76

A

C

ATOM

315

NE1

TRP

A

43

−43.304

−56.972

2.018

1.00

99.31

A

N

ATOM

316

CE2

TRP

A

43

−42.741

−56.766

3.251

1.00

100.88

A

C

ATOM

317

CD2

TRP

A

43

−42.994

−55.428

3.613

1.00

101.34

A

C

ATOM

318

CE3

TRP

A

43

−42.516

−54.953

4.849

1.00

100.31

A

C

ATOM

319

CZ3

TRP

A

43

−41.815

−55.811

5.661

1.00

100.06

A

C

ATOM

320

CH2

TRP

A

43

−41.579

−57.142

5.276

1.00

101.07

A

C

ATOM

321

CZ2

TRP

A

43

−42.031

−57.638

4.078

1.00

101.17

A

C

ATOM

322

C

TRP

A

43

−45.127

−51.714

4.106

1.00

101.22

A

C

ATOM

323

O

TRP

A

43

−44.188

−51.358

4.818

1.00

101.16

A

O

ATOM

324

N

VAL

A

44

−46.069

−50.877

3.686

1.00

102.17

A

N

ATOM

325

CA

VAL

A

44

−46.094

−49.485

4.111

1.00

103.15

A

C

ATOM

326

CB

VAL

A

44

−46.727

−48.574

3.043

1.00

102.97

A

C

ATOM

327

CG1

VAL

A

44

−46.855

−47.156

3.550

1.00

103.29

A

C

ATOM

328

CG2

VAL

A

44

−45.874

−48.572

1.797

1.00

103.24

A

C

ATOM

329

C

VAL

A

44

−46.840

−49.420

5.438

1.00

104.12

A

C

ATOM

330

O

VAL

A

44

−46.401

−48.750

6.374

1.00

104.27

A

O

ATOM

331

N

CYS

A

45

−47.956

−50.145

5.508

1.00

105.17

A

N

ATOM

332

CA

CYS

A

45

−48.631

−50.450

6.757

1.00

106.25

A

C

ATOM

333

CB

CYS

A

45

−49.593

−51.611

6.541

1.00

106.20

A

C

ATOM

334

SG

CYS

A

45

−51.076

−51.211

5.617

1.00

106.20

A

S

ATOM

335

C

CYS

A

45

−47.640

−50.845

7.842

1.00

107.29

A

C

ATOM

336

O

CYS

A

45

−47.870

−50.597

9.021

1.00

107.60

A

O

ATOM

337

N

GLU

A

46

−46.545

−51.473

7.435

1.00

108.69

A

N

ATOM

338

CA

GLU

A

46

−45.515

−51.916

8.360

1.00

110.24

A

C

ATOM

339

CB

GLU

A

46

−44.612

−52.965

7.713

1.00

110.23

A

C

ATOM

340

CG

GLU

A

46

−45.138

−54.386

7.811

1.00

110.85

A

C

ATOM

341

CD

GLU

A

46

−44.997

−54.968

9.203

1.00

111.43

A

C

ATOM

342

OE1

GLU

A

46

−44.313

−54.353

10.047

1.00

112.67

A

O

ATOM

343

OE2

GLU

A

46

−45.575

−56.043

9.453

1.00

111.35

A

O

ATOM

344

C

GLU

A

46

−44.670

−50.787

8.917

1.00

111.35

A

C

ATOM

345

O

GLU

A

46

−44.439

−50.744

10.123

1.00

111.81

A

O

ATOM

346

N

GLU

A

47

−44.199

−49.887

8.053

1.00

112.63

A

N

ATOM

347

CA

GLU

A

47

−43.356

−48.777

8.498

1.00

114.09

A

C

ATOM

348

CB

GLU

A

47

−42.759

−48.016

7.323

1.00

114.16

A

C

ATOM

349

CG

GLU

A

47

−42.008

−48.818

6.296

1.00

115.52

A

C

ATOM

350

CD

GLU

A

47

−42.234

−48.247

4.902

1.00

117.58

A

C

ATOM

351

OE1

GLU

A

47

−43.237

−48.643

4.268

1.00

118.42

A

O

ATOM

352

OE2

GLU

A

47

−41.438

−47.390

4.449

1.00

117.72

A

O

ATOM

353

C

GLU

A

47

−44.158

−47.786

9.331

1.00

114.91

A

C

ATOM

354

O

GLU

A

47

−43.627

−47.144

10.241

1.00

115.34

A

O

ATOM

355

N

ILE

A

48

−45.432

−47.643

8.998

1.00

115.80

A

N

ATOM

356

CA

ILE

A

48

−46.292

−46.700

9.686

1.00

116.71

A

C

ATOM

357

CB

ILE

A

48

−47.101

−45.823

8.690

1.00

116.52

A

C

ATOM

358

CG1

ILE

A

48

−46.208

−45.294

7.556

1.00

115.94

A

C

ATOM

359

CD1

ILE

A

48

−45.167

−44.282

7.970

1.00

115.72

A

C

ATOM

360

CG2

ILE

A

48

−47.856

−44.708

9.423

1.00

116.26

A

C

ATOM

361

C

ILE

A

48

−47.236

−47.452

10.629

1.00

117.74

A

C

ATOM

362

O

ILE

A

48

−48.272

−47.977

10.193

1.00

117.86

A

O

ATOM

363

N

PRO

A

49

−46.887

−47.500

11.930

1.00

118.61

A

N

ATOM

364

CA

PRO

A

49

−47.802

−48.069

12.916

1.00

119.18

A

C

ATOM

365

CB

PRO

A

49

−47.275

−47.512

14.246

1.00

119.38

A

C

ATOM

366

CG

PRO

A

49

−46.305

−46.392

13.863

1.00

119.07

A

C

ATOM

367

CD

PRO

A

49

−45.727

−46.862

12.577

1.00

118.70

A

C

ATOM

368

C

PRO

A

49

−49.228

−47.577

12.667

1.00

119.74

A

C

ATOM

369

O

PRO

A

49

−50.156

−48.387

12.601

1.00

119.68

A

O

ATOM

370

N

ASP

A

50

−49.374

−46.260

12.493

1.00

120.42

A

N

ATOM

371

CA

ASP

A

50

−50.673

−45.623

12.236

1.00

121.04

A

C

ATOM

372

CB

ASP

A

50

−50.536

−44.097

12.198

1.00

120.95

A

C

ATOM

373

CG

ASP

A

50

−50.319

−43.497

13.572

1.00

121.28

A

C

ATOM

374

OD1

ASP

A

50

−50.936

−43.992

14.541

1.00

122.39

A

O

ATOM

375

OD2

ASP

A

50

−49.540

−42.525

13.683

1.00

120.68

A

O

ATOM

376

C

ASP

A

50

−51.377

−46.112

10.971

1.00

121.39

A

C

ATOM

377

O

ASP

A

50

−52.587

−46.337

10.984

1.00

121.26

A

O

ATOM

378

N

LEU

A

51

−50.635

−46.275

9.879

1.00

121.82

A

N

ATOM

379

CA

LEU

A

51

−51.291

−46.624

8.632

1.00

122.30

A

C

ATOM

380

CB

LEU

A

51

−50.338

−46.623

7.437

1.00

122.31

A

C

ATOM

381

CG

LEU

A

51

−51.042

−46.766

6.079

1.00

122.00

A

C

ATOM

382

CD1

LEU

A

51

−51.829

−45.526

5.728

1.00

121.37

A

C

ATOM

383

CD2

LEU

A

51

−50.043

−47.072

4.989

1.00

122.10

A

C

ATOM

384

C

LEU

A

51

−52.013

−47.948

8.762

1.00

122.66

A

C

ATOM

385

O

LEU

A

51

−53.193

−48.027

8.453

1.00

122.67

A

O

ATOM

386

N

LYS

A

52

−51.318

−48.976

9.243

1.00

123.23

A

N

ATOM

387

CA

LYS

A

52

−51.953

−50.277

9.420

1.00

123.97

A

C

ATOM

388

CB

LYS

A

52

−50.941

−51.358

9.837

1.00

123.77

A

C

ATOM

389

CG

LYS

A

52

−51.479

−52.784

9.663

1.00

123.55

A

C

ATOM

390

CD

LYS

A

52

−50.397

−53.852

9.492

1.00

122.52

A

C

ATOM

391

CE

LYS

A

52

−51.038

−55.199

9.103

1.00

121.97

A

C

ATOM

392

NZ

LYS

A

52

−50.057

−56.277

8.787

1.00

120.64

A

N

ATOM

393

C

LYS

A

52

−53.088

−50.134

10.434

1.00

124.64

A

C

ATOM

394

O

LYS

A

52

−54.096

−50.856

10.372

1.00

124.65

A

O

ATOM

395

N

LEU

A

53

−52.918

−49.167

11.337

1.00

125.35

A

N

ATOM

396

CA

LEU

A

53

−53.910

−48.848

12.359

1.00

126.04

A

C

ATOM

397

CB

LEU

A

53

−53.290

−47.925

13.416

1.00

125.94

A

C

ATOM

398

CG

LEU

A

53

−53.937

−47.662

14.780

1.00

125.95

A

C

ATOM

399

CD1

LEU

A

53

−54.465

−48.937

15.426

1.00

125.92

A

C

ATOM

400

CD2

LEU

A

53

−52.940

−46.951

15.699

1.00

125.02

A

C

ATOM

401

C

LEU

A

53

−55.158

−48.226

11.737

1.00

126.53

A

C

ATOM

402

O

LEU

A

53

−56.265

−48.468

12.206

1.00

126.58

A

O

ATOM

403

N

ALA

A

54

−54.963

−47.441

10.675

1.00

127.36

A

N

ATOM

404

CA

ALA

A

54

−56.058

−46.870

9.875

1.00

127.99

A

C

ATOM

405

CB

ALA

A

54

−55.656

−45.516

9.330

1.00

127.67

A

C

ATOM

406

C

ALA

A

54

−56.465

−47.795

8.726

1.00

128.65

A

C

ATOM

407

O

ALA

A

54

−57.326

−47.447

7.915

1.00

128.47

A

O

ATOM

408

N

MET

A

55

−55.839

−48.972

8.667

1.00

129.68

A

N

ATOM

409

CA

MET

A

55

−56.079

−49.940

7.601

1.00

130.70

A

C

ATOM

410

CB

MET

A

55

−54.786

−50.201

6.815

1.00

130.51

A

C

ATOM

411

CG

MET

A

55

−54.384

−49.101

5.821

1.00

129.74

A

C

ATOM

412

SD

MET

A

55

−55.569

−48.795

4.492

1.00

127.39

A

S

ATOM

413

CE

MET

A

55

−55.325

−50.215

3.440

1.00

127.90

A

C

ATOM

414

C

MET

A

55

−56.671

−51.266

8.102

1.00

131.78

A

C

ATOM

415

O

MET

A

55

−56.973

−52.158

7.295

1.00

131.85

A

O

ATOM

416

N

GLU

A

56

−56.853

−51.387

9.422

1.00

133.02

A

N

ATOM

417

CA

GLU

A

56

−57.356

−52.631

10.045

1.00

134.07

A

C

ATOM

418

CB

GLU

A

56

−57.164

−52.596

11.570

1.00

134.37

A

C

ATOM

419

CG

GLU

A

56

−57.099

−53.987

12.225

1.00

135.95

A

C

ATOM

420

CD

GLU

A

56

−56.952

−53.938

13.743

1.00

137.82

A

C

ATOM

421

OE1

GLU

A

56

−57.895

−54.388

14.438

1.00

138.95

A

O

ATOM

422

OE2

GLU

A

56

−55.904

−53.454

14.241

1.00

138.31

A

O

ATOM

423

C

GLU

A

56

−58.819

−52.943

9.689

1.00

134.24

A

C

ATOM

424

O

GLU

A

56

−59.578

−53.476

10.512

1.00

134.24

A

O

ATOM

425

N

ASN

A

57

−59.190

−52.624

8.449

1.00

134.47

A

N

ATOM

426

CA

ASN

A

57

−60.555

−52.782

7.954

1.00

134.61

A

C

ATOM

427

CB

ASN

A

57

−61.045

−51.466

7.362

1.00

134.62

A

C

ATOM

428

CG

ASN

A

57

−60.630

−50.273

8.195

1.00

134.91

A

C

ATOM

429

OD1

ASN

A

57

−61.277

−49.944

9.189

1.00

135.62

A

O

ATOM

430

ND2

ASN

A

57

−59.540

−49.621

7.798

1.00

134.76

A

N

ATOM

431

C

ASN

A

57

−60.640

−53.893

6.919

1.00

134.61

A

C

ATOM

432

O

ASN

A

57

−61.608

−54.663

6.900

1.00

134.57

A

O

ATOM

433

N

TYR

A

58

−59.621

−53.955

6.059

1.00

134.64

A

N

ATOM

434

CA

TYR

A

58

−59.455

−55.038

5.085

1.00

134.67

A

C

ATOM

435

CB

TYR

A

58

−59.885

−54.602

3.672

1.00

134.65

A

C

ATOM

436

CG

TYR

A

58

−61.314

−54.090

3.576

1.00

134.28

A

C

ATOM

437

CD1

TYR

A

58

−61.576

−52.720

3.476

1.00

133.84

A

C

ATOM

438

CE1

TYR

A

58

−62.885

−52.239

3.392

1.00

133.72

A

C

ATOM

439

CZ

TYR

A

58

−63.949

−53.131

3.410

1.00

133.33

A

C

ATOM

440

OH

TYR

A

58

−65.239

−52.647

3.332

1.00

132.59

A

O

ATOM

441

CE2

TYR

A

58

−63.716

−54.500

3.507

1.00

133.40

A

C

ATOM

442

CD2

TYR

A

58

−62.401

−54.973

3.590

1.00

133.57

A

C

ATOM

443

C

TYR

A

58

−58.004

−55.513

5.073

1.00

134.65

A

C

ATOM

444

O

TYR

A

58

−57.075

−54.723

5.264

1.00

134.50

A

O

ATOM

445

N

ILE

A

61

−58.230

−60.096

2.529

1.00

148.19

A

N

ATOM

446

CA

ILE

A

61

−59.312

−60.854

1.913

1.00

148.20

A

C

ATOM

447

CB

ILE

A

61

−60.620

−59.970

1.823

1.00

148.39

A

C

ATOM

448

CG1

ILE

A

61

−61.918

−60.819

1.881

1.00

148.59

A

C

ATOM

449

CD1

ILE

A

61

−62.314

−61.569

0.604

1.00

149.13

A

C

ATOM

450

CG2

ILE

A

61

−60.536

−58.923

0.686

1.00

148.44

A

C

ATOM

451

C

ILE

A

61

−58.885

−61.477

0.564

1.00

147.98

A

C

ATOM

452

O

ILE

A

61

−59.506

−62.438

0.098

1.00

148.04

A

O

ATOM

453

N

ASP

A

62

−57.792

−60.957

−0.013

1.00

147.69

A

N

ATOM

454

CA

ASP

A

62

−57.357

−61.249

−1.401

1.00

147.18

A

C

ATOM

455

CB

ASP

A

62

−56.754

−62.655

−1.557

1.00

147.32

A

C

ATOM

456

CG

ASP

A

62

−55.253

−62.683

−1.296

1.00

147.99

A

C

ATOM

457

OD1

ASP

A

62

−54.859

−62.802

−0.119

1.00

148.20

A

O

ATOM

458

OD2

ASP

A

62

−54.463

−62.613

−2.268

1.00

148.70

A

O

ATOM

459

C

ASP

A

62

−58.499

−61.030

−2.389

1.00

146.54

A

C

ATOM

460

O

ASP

A

62

−58.990

−61.977

−3.022

1.00

146.57

A

O

ATOM

461

N

TYR

A

63

−58.919

−59.772

−2.506

1.00

145.52

A

N

ATOM

462

CA

TYR

A

63

−60.147

−59.451

−3.212

1.00

144.43

A

C

ATOM

463

CB

TYR

A

63

−60.747

−58.128

−2.707

1.00

144.60

A

C

ATOM

464

CG

TYR

A

63

−62.252

−58.201

−2.506

1.00

144.65

A

C

ATOM

465

CD1

TYR

A

63

−62.860

−59.383

−2.070

1.00

144.40

A

C

ATOM

466

CE1

TYR

A

63

−64.235

−59.469

−1.897

1.00

144.58

A

C

ATOM

467

CZ

TYR

A

63

−65.027

−58.360

−2.149

1.00

145.01

A

C

ATOM

468

OH

TYR

A

63

−66.392

−58.445

−1.969

1.00

144.94

A

O

ATOM

469

CE2

TYR

A

63

−64.451

−57.168

−2.577

1.00

145.08

A

C

ATOM

470

CD2

TYR

A

63

−63.066

−57.095

−2.751

1.00

144.97

A

C

ATOM

471

C

TYR

A

63

−59.966

−59.481

−4.726

1.00

143.49

A

C

ATOM

472

O

TYR

A

63

−58.926

−59.074

−5.238

1.00

143.40

A

O

ATOM

473

N

ASP

A

64

−60.993

−59.987

−5.410

1.00

142.39

A

N

ATOM

474

CA

ASP

A

64

−61.014

−60.204

−6.866

1.00

141.30

A

C

ATOM

475

CB

ASP

A

64

−62.426

−59.996

−7.420

1.00

141.47

A

C

ATOM

476

CG

ASP

A

64

−63.438

−60.951

−6.804

1.00

141.89

A

C

ATOM

477

OD1

ASP

A

64

−64.543

−60.491

−6.432

1.00

142.30

A

O

ATOM

478

OD2

ASP

A

64

−63.122

−62.160

−6.678

1.00

141.76

A

O

ATOM

479

C

ASP

A

64

−59.996

−59.389

−7.644

1.00

140.30

A

C

ATOM

480

O

ASP

A

64

−60.279

−58.280

−8.104

1.00

140.13

A

O

ATOM

481

N

THR

A

65

−58.810

−59.972

−7.786

1.00

138.98

A

N

ATOM

482

CA

THR

A

65

−57.651

−59.287

−8.337

1.00

137.84

A

C

ATOM

483

CB

THR

A

65

−56.343

−60.030

−7.983

1.00

137.94

A

C

ATOM

484

OG1

THR

A

65

−56.081

−61.041

−8.961

1.00

138.14

A

O

ATOM

485

CG2

THR

A

65

−56.435

−60.677

−6.598

1.00

138.08

A

C

ATOM

486

C

THR

A

65

−57.752

−59.097

−9.851

1.00

136.91

A

C

ATOM

487

O

THR

A

65

−56.923

−58.414

−10.454

1.00

136.74

A

O

ATOM

488

N

LYS

A

66

−58.771

−59.706

−10.455

1.00

135.77

A

N

ATOM

489

CA

LYS

A

66

−59.036

−59.548

−11.887

1.00

134.47

A

C

ATOM

490

CB

LYS

A

66

−59.508

−60.876

−12.506

1.00

134.55

A

C

ATOM

491

CG

LYS

A

66

−58.377

−61.747

−13.098

1.00

134.51

A

C

ATOM

492

CD

LYS

A

66

−58.017

−61.360

−14.544

1.00

133.99

A

C

ATOM

493

CE

LYS

A

66

−57.176

−60.081

−14.628

1.00

133.79

A

C

ATOM

494

NZ

LYS

A

66

−57.313

−59.355

−15.926

1.00

133.20

A

N

ATOM

495

C

LYS

A

66

−60.020

−58.411

−12.193

1.00

133.48

A

C

ATOM

496

O

LYS

A

66

−60.388

−58.199

−13.351

1.00

133.37

A

O

ATOM

497

N

SER

A

67

−60.420

−57.681

−11.151

1.00

132.18

A

N

ATOM

498

CA

SER

A

67

−61.353

−56.561

−11.273

1.00

130.89

A

C

ATOM

499

CB

SER

A

67

−62.492

−56.716

−10.267

1.00

131.02

A

C

ATOM

500

OG

SER

A

67

−63.173

−55.483

−10.089

1.00

130.86

A

O

ATOM

501

C

SER

A

67

−60.688

−55.205

−11.060

1.00

129.93

A

C

ATOM

502

O

SER

A

67

−59.815

−55.064

−10.215

1.00

129.93

A

O

ATOM

503

N

PHE

A

68

−61.106

−54.210

−11.833

1.00

128.71

A

N

ATOM

504

CA

PHE

A

68

−60.701

−52.832

−11.579

1.00

127.56

A

C

ATOM

505

CB

PHE

A

68

−60.754

−52.005

−12.865

1.00

127.51

A

C

ATOM

506

CG

PHE

A

68

−60.508

−50.535

−12.657

1.00

126.77

A

C

ATOM

507

CD1

PHE

A

68

−59.225

−50.013

−12.736

1.00

126.68

A

C

ATOM

508

CE1

PHE

A

68

−58.995

−48.650

−12.553

1.00

126.24

A

C

ATOM

509

CZ

PHE

A

68

−60.057

−47.798

−12.280

1.00

125.65

A

C

ATOM

510

CE2

PHE

A

68

−61.338

−48.308

−12.197

1.00

125.60

A

C

ATOM

511

CD2

PHE

A

68

−61.560

−49.671

−12.389

1.00

126.17

A

C

ATOM

512

C

PHE

A

68

−61.644

−52.251

−10.535

1.00

126.83

A

C

ATOM

513

O

PHE

A

68

−61.224

−51.553

−9.613

1.00

126.82

A

O

ATOM

514

N

GLU

A

69

−62.925

−52.562

−10.696

1.00

125.85

A

N

ATOM

515

CA

GLU

A

69

−63.985

−52.135

−9.780

1.00

124.96

A

C

ATOM

516

CB

GLU

A

69

−65.349

−52.732

−10.216

1.00

125.21

A

C

ATOM

517

CG

GLU

A

69

−65.677

−52.671

−11.733

1.00

125.76

A

C

ATOM

518

CD

GLU

A

69

−65.053

−53.818

−12.551

1.00

126.64

A

C

ATOM

519

OE1

GLU

A

69

−64.224

−53.533

−13.447

1.00

126.56

A

O

ATOM

520

OE2

GLU

A

69

−65.387

−55.000

−12.299

1.00

126.55

A

O

ATOM

521

C

GLU

A

69

−63.675

−52.528

−8.322

1.00

123.89

A

C

ATOM

522

O

GLU

A

69

−64.465

−52.257

−7.413

1.00

123.86

A

O

ATOM

523

N

SER

A

70

−62.522

−53.158

−8.109

1.00

122.30

A

N

ATOM

524

CA

SER

A

70

−62.179

−53.714

−6.818

1.00

120.96

A

C

ATOM

525

CB

SER

A

70

−62.380

−55.226

−6.851

1.00

120.95

A

C

ATOM

526

OG

SER

A

70

−62.289

−55.789

−5.560

1.00

121.35

A

O

ATOM

527

C

SER

A

70

−60.745

−53.374

−6.422

1.00

120.04

A

C

ATOM

528

O

SER

A

70

−60.439

−53.207

−5.240

1.00

119.98

A

O

ATOM

529

N

MET

A

71

−59.866

−53.280

−7.412

1.00

118.79

A

N

ATOM

530

CA

MET

A

71

−58.463

−52.977

−7.159

1.00

117.61

A

C

ATOM

531

CB

MET

A

71

−57.576

−53.543

−8.271

1.00

117.56

A

C

ATOM

532

CG

MET

A

71

−57.391

−55.068

−8.245

1.00

116.29

A

C

ATOM

533

SD

MET

A

71

−56.669

−55.748

−6.732

1.00

113.64

A

S

ATOM

534

CE

MET

A

71

−55.114

−54.860

−6.643

1.00

112.92

A

C

ATOM

535

C

MET

A

71

−58.259

−51.475

−7.012

1.00

117.17

A

C

ATOM

536

O

MET

A

71

−57.283

−51.019

−6.420

1.00

116.71

A

O

ATOM

537

N

GLN

A

72

−59.191

−50.714

−7.572

1.00

116.80

A

N

ATOM

538

CA

GLN

A

72

−59.270

−49.286

−7.329

1.00

116.52

A

C

ATOM

539

CB

GLN

A

72

−60.106

−48.623

−8.424

1.00

116.59

A

C

ATOM

540

CG

GLN

A

72

−59.881

−47.128

−8.588

1.00

117.08

A

C

ATOM

541

CD

GLN

A

72

−61.111

−46.409

−9.136

1.00

118.53

A

C

ATOM

542

OE1

GLN

A

72

−62.196

−46.995

−9.267

1.00

118.51

A

O

ATOM

543

NE2

GLN

A

72

−60.948

−45.125

−9.446

1.00

119.22

A

N

ATOM

544

C

GLN

A

72

−59.915

−49.080

−5.956

1.00

116.11

A

C

ATOM

545

O

GLN

A

72

−59.471

−48.246

−5.152

1.00

115.82

A

O

ATOM

546

N

ARG

A

73

−60.950

−49.875

−5.691

1.00

115.62

A

N

ATOM

547

CA

ARG

A

73

−61.693

−49.802

−4.441

1.00

115.33

A

C

ATOM

548

CB

ARG

A

73

−62.965

−50.658

−4.531

1.00

115.64

A

C

ATOM

549

CG

ARG

A

73

−64.200

−50.065

−3.826

1.00

117.14

A

C

ATOM

550

CD

ARG

A

73

−65.496

−50.844

−4.136

1.00

119.28

A

C

ATOM

551

NE

ARG

A

73

−65.366

−52.268

−3.819

1.00

122.02

A

N

ATOM

552

CZ

ARG

A

73

−66.206

−53.225

−4.217

1.00

123.79

A

C

ATOM

553

NH1

ARG

A

73

−67.270

−52.921

−4.957

1.00

124.79

A

N

ATOM

554

NH2

ARG

A

73

−65.977

−54.496

−3.874

1.00

123.72

A

N

ATOM

555

C

ARG

A

73

−60.825

−50.221

−3.250

1.00

114.60

A

C

ATOM

556

O

ARG

A

73

−61.312

−50.310

−2.120

1.00

114.81

A

O

ATOM

557

N

LEU

A

74

−59.542

−50.472

−3.517

1.00

113.56

A

N

ATOM

558

CA

LEU

A

74

−58.548

−50.772

−2.483

1.00

112.50

A

C

ATOM

559

CB

LEU

A

74

−57.975

−52.183

−2.671

1.00

112.27

A

C

ATOM

560

CG

LEU

A

74

−56.625

−52.539

−2.031

1.00

111.68

A

C

ATOM

561

CD1

LEU

A

74

−56.709

−52.637

−0.512

1.00

111.80

A

C

ATOM

562

CD2

LEU

A

74

−56.106

−53.829

−2.597

1.00

110.94

A

C

ATOM

563

C

LEU

A

74

−57.425

−49.737

−2.489

1.00

112.02

A

C

ATOM

564

O

LEU

A

74

−56.933

−49.335

−1.438

1.00

111.93

A

O

ATOM

565

N

CYS

A

75

−57.016

−49.319

−3.677

1.00

111.48

A

N

ATOM

566

CA

CYS

A

75

−55.961

−48.338

−3.806

1.00

111.08

A

C

ATOM

567

CB

CYS

A

75

−55.688

−48.051

−5.272

1.00

111.07

A

C

ATOM

568

SG

CYS

A

75

−54.815

−49.361

−6.060

1.00

110.05

A

S

ATOM

569

C

CYS

A

75

−56.325

−47.053

−3.101

1.00

111.15

A

C

ATOM

570

O

CYS

A

75

−55.531

−46.517

−2.337

1.00

111.18

A

O

ATOM

571

N

ASP

A

76

−57.531

−46.561

−3.368

1.00

111.26

A

N

ATOM

572

CA

ASP

A

76

−58.008

−45.313

−2.774

1.00

111.06

A

C

ATOM

573

CB

ASP

A

76

−59.288

−44.831

−3.461

1.00

111.36

A

C

ATOM

574

CG

ASP

A

76

−59.208

−44.933

−4.977

1.00

111.91

A

C

ATOM

575

OD1

ASP

A

76

−58.151

−44.566

−5.549

1.00

112.24

A

O

ATOM

576

OD2

ASP

A

76

−60.205

−45.384

−5.586

1.00

112.26

A

O

ATOM

577

C

ASP

A

76

−58.220

−45.487

−1.283

1.00

110.53

A

C

ATOM

578

O

ASP

A

76

−57.856

−44.613

−0.513

1.00

110.53

A

O

ATOM

579

N

LYS

A

77

−58.781

−46.625

−0.880

1.00

109.92

A

N

ATOM

580

CA

LYS

A

77

−58.816

−46.993

0.526

1.00

109.58

A

C

ATOM

581

CB

LYS

A

77

−59.188

−48.465

0.684

1.00

109.53

A

C

ATOM

582

CG

LYS

A

77

−59.979

−48.772

1.945

1.00

110.76

A

C

ATOM

583

CD

LYS

A

77

−59.103

−48.936

3.197

1.00

112.28

A

C

ATOM

584

CE

LYS

A

77

−59.903

−48.725

4.493

1.00

113.11

A

C

ATOM

585

NZ

LYS

A

77

−61.147

−49.565

4.594

1.00

113.39

A

N

ATOM

586

C

LYS

A

77

−57.455

−46.702

1.172

1.00

109.25

A

C

ATOM

587

O

LYS

A

77

−57.389

−46.067

2.222

1.00

109.34

A

O

ATOM

588

N

TYR

A

78

−56.382

−47.150

0.522

1.00

108.83

A

N

ATOM

589

CA

TYR

A

78

−55.015

−46.878

0.959

1.00

108.46

A

C

ATOM

590

CB

TYR

A

78

−54.036

−47.844

0.268

1.00

108.12

A

C

ATOM

591

CG

TYR

A

78

−52.618

−47.325

0.098

1.00

106.86

A

C

ATOM

592

CD1

TYR

A

78

−51.616

−47.659

1.009

1.00

105.78

A

C

ATOM

593

CE1

TYR

A

78

−50.307

−47.177

0.855

1.00

104.19

A

C

ATOM

594

CZ

TYR

A

78

−49.996

−46.365

−0.221

1.00

103.25

A

C

ATOM

595

OH

TYR

A

78

−48.721

−45.894

−0.377

1.00

101.64

A

O

ATOM

596

CE2

TYR

A

78

−50.970

−46.017

−1.137

1.00

104.51

A

C

ATOM

597

CD2

TYR

A

78

−52.273

−46.504

−0.980

1.00

105.78

A

C

ATOM

598

C

TYR

A

78

−54.612

−45.423

0.704

1.00

108.79

A

C

ATOM

599

O

TYR

A

78

−54.011

−44.782

1.565

1.00

108.98

A

O

ATOM

600

N

ASN

A

79

−54.927

−44.909

−0.483

1.00

109.03

A

N

ATOM

601

CA

ASN

A

79

−54.532

−43.551

−0.872

1.00

109.17

A

C

ATOM

602

CB

ASN

A

79

−54.911

−43.273

−2.326

1.00

109.16

A

C

ATOM

603

CG

ASN

A

79

−53.888

−43.788

−3.296

1.00

108.66

A

C

ATOM

604

OD1

ASN

A

79

−52.823

−43.204

−3.452

1.00

108.38

A

O

ATOM

605

ND2

ASN

A

79

−54.208

−44.883

−3.965

1.00

108.29

A

N

ATOM

606

C

ASN

A

79

−55.137

−42.478

0.024

1.00

109.32

A

C

ATOM

607

O

ASN

A

79

−54.520

−41.436

0.266

1.00

109.26

A

O

ATOM

608

N

ARG

A

80

−56.352

−42.746

0.498

1.00

109.42

A

N

ATOM

609

CA

ARG

A

80

−57.021

−41.887

1.461

1.00

109.53

A

C

ATOM

610

CB

ARG

A

80

−58.486

−42.304

1.651

1.00

109.47

A

C

ATOM

611

CG

ARG

A

80

−59.354

−42.115

0.427

1.00

109.65

A

C

ATOM

612

CD

ARG

A

80

−60.823

−42.087

0.778

1.00

110.68

A

C

ATOM

613

NE

ARG

A

80

−61.471

−43.396

0.758

1.00

111.79

A

N

ATOM

614

CZ

ARG

A

80

−61.977

−43.973

−0.331

1.00

112.65

A

C

ATOM

615

NH1

ARG

A

80

−61.891

−43.370

−1.516

1.00

113.21

A

N

ATOM

616

NH2

ARG

A

80

−62.562

−45.163

−0.238

1.00

112.70

A

N

ATOM

617

C

ARG

A

80

−56.262

−41.986

2.774

1.00

109.55

A

C

ATOM

618

O

ARG

A

80

−55.782

−40.975

3.310

1.00

109.50

A

O

ATOM

619

N

ALA

A

81

−56.137

−43.219

3.260

1.00

109.52

A

N

ATOM

620

CA

ALA

A

81

−55.428

−43.514

4.492

1.00

109.61

A

C

ATOM

621

CB

ALA

A

81

−55.173

−45.003

4.596

1.00

109.59

A

C

ATOM

622

C

ALA

A

81

−54.123

−42.727

4.593

1.00

109.65

A

C

ATOM

623

O

ALA

A

81

−53.861

−42.082

5.606

1.00

109.66

A

O

ATOM

624

N

ILE

A

82

−53.335

−42.758

3.525

1.00

109.87

A

N

ATOM

625

CA

ILE

A

82

−52.070

−42.032

3.458

1.00

110.27

A

C

ATOM

626

CB

ILE

A

82

−51.390

−42.233

2.086

1.00

110.13

A

C

ATOM

627

CG1

ILE

A

82

−50.775

−43.631

2.008

1.00

110.39

A

C

ATOM

628

CD1

ILE

A

82

−49.630

−43.881

2.984

1.00

110.23

A

C

ATOM

629

CG2

ILE

A

82

−50.324

−41.176

1.821

1.00

109.85

A

C

ATOM

630

C

ILE

A

82

−52.227

−40.550

3.763

1.00

110.67

A

C

ATOM

631

O

ILE

A

82

−51.499

−40.001

4.589

1.00

110.56

A

O

ATOM

632

N

ASP

A

83

−53.182

−39.909

3.099

1.00

111.41

A

N

ATOM

633

CA

ASP

A

83

−53.382

−38.481

3.266

1.00

112.09

A

C

ATOM

634

CB

ASP

A

83

−54.531

−37.987

2.384

1.00

111.72

A

C

ATOM

635

CG

ASP

A

83

−54.178

−37.996

0.898

1.00

111.20

A

C

ATOM

636

OD1

ASP

A

83

−53.023

−37.679

0.524

1.00

109.51

A

O

ATOM

637

OD2

ASP

A

83

−55.071

−38.318

0.095

1.00

111.13

A

O

ATOM

638

C

ASP

A

83

−53.630

−38.198

4.734

1.00

112.82

A

C

ATOM

639

O

ASP

A

83

−52.987

−37.333

5.332

1.00

112.77

A

O

ATOM

640

N

SER

A

84

−54.528

−38.982

5.318

1.00

113.99

A

N

ATOM

641

CA

SER

A

84

−54.825

−38.896

6.735

1.00

115.04

A

C

ATOM

642

CB

SER

A

84

−55.782

−40.003

7.159

1.00

114.86

A

C

ATOM

643

OG

SER

A

84

−56.097

−39.858

8.526

1.00

115.17

A

O

ATOM

644

C

SER

A

84

−53.561

−38.940

7.580

1.00

115.81

A

C

ATOM

645

O

SER

A

84

−53.458

−38.212

8.556

1.00

116.25

A

O

ATOM

646

N

ILE

A

85

−52.600

−39.779

7.209

1.00

116.79

A

N

ATOM

647

CA

ILE

A

85

−51.319

−39.798

7.917

1.00

117.76

A

C

ATOM

648

CB

ILE

A

85

−50.387

−40.972

7.477

1.00

117.66

A

C

ATOM

649

CG1

ILE

A

85

−51.134

−42.305

7.423

1.00

117.67

A

C

ATOM

650

CD1

ILE

A

85

−51.749

−42.753

8.737

1.00

118.16

A

C

ATOM

651

CG2

ILE

A

85

−49.181

−41.085

8.400

1.00

117.67

A

C

ATOM

652

C

ILE

A

85

−50.591

−38.478

7.688

1.00

118.51

A

C

ATOM

653

O

ILE

A

85

−50.081

−37.875

8.628

1.00

118.56

A

O

ATOM

654

N

HIS

A

86

−50.559

−38.033

6.435

1.00

119.49

A

N

ATOM

655

CA

HIS

A

86

−49.768

−36.872

6.062

1.00

120.42

A

C

ATOM

656

CB

HIS

A

86

−49.645

−36.755

4.553

1.00

120.44

A

C

ATOM

657

CG

HIS

A

86

−48.533

−37.576

3.997

1.00

120.44

A

C

ATOM

658

ND1

HIS

A

86

−48.749

−38.739

3.295

1.00

120.34

A

N

ATOM

659

CE1

HIS

A

86

−47.587

−39.262

2.949

1.00

120.27

A

C

ATOM

660

NE2

HIS

A

86

−46.624

−38.489

3.419

1.00

120.05

A

N

ATOM

661

CD2

HIS

A

86

−47.190

−37.429

4.081

1.00

120.58

A

C

ATOM

662

C

HIS

A

86

−50.306

−35.597

6.643

1.00

121.22

A

C

ATOM

663

O

HIS

A

86

−49.544

−34.660

6.876

1.00

121.40

A

O

ATOM

664

N

GLN

A

87

−51.615

−35.560

6.877

1.00

122.16

A

N

ATOM

665

CA

GLN

A

87

−52.204

−34.462

7.629

1.00

123.16

A

C

ATOM

666

CB

GLN

A

87

−53.743

−34.520

7.633

1.00

123.21

A

C

ATOM

667

CG

GLN

A

87

−54.441

−33.836

6.427

1.00

122.96

A

C

ATOM

668

CD

GLN

A

87

−53.996

−32.384

6.176

1.00

122.88

A

C

ATOM

669

OE1

GLN

A

87

−53.924

−31.565

7.092

1.00

122.57

A

O

ATOM

670

NE2

GLN

A

87

−53.708

−32.068

4.922

1.00

123.70

A

N

ATOM

671

C

GLN

A

87

−51.632

−34.449

9.051

1.00

123.82

A

C

ATOM

672

O

GLN

A

87

−51.205

−33.405

9.540

1.00

123.82

A

O

ATOM

673

N

LEU

A

88

−51.588

−35.619

9.686

1.00

124.72

A

N

ATOM

674

CA

LEU

A

88

−51.017

−35.769

11.032

1.00

125.70

A

C

ATOM

675

CB

LEU

A

88

−51.103

−37.233

11.464

1.00

125.65

A

C

ATOM

676

CG

LEU

A

88

−51.652

−37.556

12.849

1.00

125.34

A

C

ATOM

677

CD1

LEU

A

88

−52.315

−38.923

12.805

1.00

124.92

A

C

ATOM

678

CD2

LEU

A

88

−50.557

−37.508

13.901

1.00

124.77

A

C

ATOM

679

C

LEU

A

88

−49.564

−35.262

11.130

1.00

126.40

A

C

ATOM

680

O

LEU

A

88

−49.204

−34.561

12.082

1.00

126.40

A

O

ATOM

681

N

TRP

A

89

−48.746

−35.612

10.139

1.00

127.23

A

N

ATOM

682

CA

TRP

A

89

−47.382

−35.098

10.017

1.00

128.22

A

C

ATOM

683

CB

TRP

A

89

−46.731

−35.612

8.722

1.00

128.29

A

C

ATOM

684

CG

TRP

A

89

−46.492

−37.123

8.620

1.00

128.38

A

C

ATOM

685

CD1

TRP

A

89

−47.028

−38.108

9.406

1.00

128.56

A

C

ATOM

686

NE1

TRP

A

89

−46.586

−39.341

8.992

1.00

127.79

A

N

ATOM

687

CE2

TRP

A

89

−45.766

−39.180

7.906

1.00

128.02

A

C

ATOM

688

CD2

TRP

A

89

−45.683

−37.797

7.640

1.00

128.22

A

C

ATOM

689

CE3

TRP

A

89

−44.889

−37.363

6.565

1.00

128.31

A

C

ATOM

690

CZ3

TRP

A

89

−44.214

−38.313

5.801

1.00

127.60

A

C

ATOM

691

CH2

TRP

A

89

−44.317

−39.678

6.095

1.00

127.75

A

C

ATOM

692

CZ2

TRP

A

89

−45.087

−40.133

7.138

1.00

128.08

A

C

ATOM

693

C

TRP

A

89

−47.342

−33.559

10.033

1.00

128.98

A

C

ATOM

694

O

TRP

A

89

−46.307

−32.968

10.341

1.00

128.91

A

O

ATOM

695

N

LYS

A

90

−48.464

−32.922

9.687

1.00

130.08

A

N

ATOM

696

CA

LYS

A

90

−48.595

−31.453

9.749

1.00

131.13

A

C

ATOM

697

CB

LYS

A

90

−49.674

−30.941

8.782

1.00

131.09

A

C

ATOM

698

CG

LYS

A

90

−49.407

−31.158

7.293

1.00

131.08

A

C

ATOM

699

CD

LYS

A

90

−50.525

−30.524

6.449

1.00

130.36

A

C

ATOM

700

CE

LYS

A

90

−50.416

−30.877

4.973

1.00

129.56

A

C

ATOM

701

NZ

LYS

A

90

−49.144

−30.412

4.359

1.00

129.04

A

N

ATOM

702

C

LYS

A

90

−48.897

−30.939

11.171

1.00

131.85

A

C

ATOM

703

O

LYS

A

90

−48.744

−29.744

11.445

1.00

131.78

A

O

ATOM

704

N

GLY

A

91

−49.345

−31.841

12.052

1.00

132.69

A

N

ATOM

705

CA

GLY

A

91

−49.537

−31.543

13.478

1.00

133.53

A

C

ATOM

706

C

GLY

A

91

−48.305

−31.927

14.281

1.00

134.21

A

C

ATOM

707

O

GLY

A

91

−47.279

−32.301

13.704

1.00

134.25

A

O

ATOM

708

N

THR

A

92

−48.400

−31.841

15.609

1.00

134.87

A

N

ATOM

709

CA

THR

A

92

−47.259

−32.142

16.494

1.00

135.45

A

C

ATOM

710

CB

THR

A

92

−47.515

−31.715

17.970

1.00

135.42

A

C

ATOM

711

OG1

THR

A

92

−48.734

−32.309

18.441

1.00

135.55

A

O

ATOM

712

CG2

THR

A

92

−47.588

−30.191

18.114

1.00

135.32

A

C

ATOM

713

C

THR

A

92

−46.908

−33.630

16.461

1.00

135.86

A

C

ATOM

714

O

THR

A

92

−47.334

−34.397

17.333

1.00

135.95

A

O

ATOM

715

N

THR

A

93

−46.148

−34.033

15.441

1.00

136.31

A

N

ATOM

716

CA

THR

A

93

−45.756

−35.440

15.253

1.00

136.73

A

C

ATOM

717

CB

THR

A

93

−46.895

−36.283

14.617

1.00

136.72

A

C

ATOM

718

OG1

THR

A

93

−48.163

−35.804

15.078

1.00

137.36

A

O

ATOM

719

CG2

THR

A

93

−46.754

−37.763

14.984

1.00

136.63

A

C

ATOM

720

C

THR

A

93

−44.486

−35.586

14.408

1.00

136.90

A

C

ATOM

721

O

THR

A

93

−44.057

−34.648

13.723

1.00

137.02

A

O

ATOM

722

N

GLN

A

94

−43.885

−36.770

14.469

1.00

136.99

A

N

ATOM

723

CA

GLN

A

94

−42.685

−37.050

13.701

1.00

137.09

A

C

ATOM

724

CB

GLN

A

94

−41.814

−38.105

14.406

1.00

137.35

A

C

ATOM

725

CG

GLN

A

94

−41.641

−37.906

15.938

1.00

138.27

A

C

ATOM

726

CD

GLN

A

94

−41.049

−36.543

16.334

1.00

139.15

A

C

ATOM

727

OE1

GLN

A

94

−41.713

−35.506

16.239

1.00

139.01

A

O

ATOM

728

NE2

GLN

A

94

−39.804

−36.554

16.806

1.00

139.46

A

N

ATOM

729

C

GLN

A

94

−43.073

−37.489

12.290

1.00

136.74

A

C

ATOM

730

O

GLN

A

94

−43.986

−38.308

12.121

1.00

136.67

A

O

ATOM

731

N

PRO

A

95

−42.388

−36.936

11.267

1.00

136.34

A

N

ATOM

732

CA

PRO

A

95

−42.684

−37.285

9.884

1.00

135.91

A

C

ATOM

733

CB

PRO

A

95

−41.927

−36.211

9.099

1.00

135.95

A

C

ATOM

734

CG

PRO

A

95

−40.738

−35.923

9.944

1.00

136.04

A

C

ATOM

735

CD

PRO

A

95

−41.250

−35.999

11.360

1.00

136.35

A

C

ATOM

736

C

PRO

A

95

−42.137

−38.671

9.538

1.00

135.52

A

C

ATOM

737

O

PRO

A

95

−41.684

−38.888

8.406

1.00

135.58

A

O

ATOM

738

N

MET

A

96

−42.196

−39.593

10.508

1.00

134.91

A

N

ATOM

739

CA

MET

A

96

−41.560

−40.914

10.422

1.00

134.21

A

C

ATOM

740

CB

MET

A

96

−42.149

−41.739

9.266

1.00

134.27

A

C

ATOM

741

CG

MET

A

96

−41.526

−43.121

9.058

1.00

134.39

A

C

ATOM

742

SD

MET

A

96

−41.574

−43.675

7.334

1.00

134.08

A

S

ATOM

743

CE

MET

A

96

−39.994

−43.078

6.730

1.00

134.28

A

C

ATOM

744

C

MET

A

96

−40.048

−40.747

10.267

1.00

133.67

A

C

ATOM

745

O

MET

A

96

−39.585

−39.908

9.487

1.00

133.79

A

O

ATOM

746

N

LYS

A

97

−39.278

−41.532

11.016

1.00

132.79

A

N

ATOM

747

CA

LYS

A

97

−37.822

−41.481

10.908

1.00

131.93

A

C

ATOM

748

CB

LYS

A

97

−37.185

−42.508

11.842

1.00

132.14

A

C

ATOM

749

CG

LYS

A

97

−35.725

−42.254

12.157

1.00

132.59

A

C

ATOM

750

CD

LYS

A

97

−35.136

−43.460

12.856

1.00

133.29

A

C

ATOM

751

CE

LYS

A

97

−33.637

−43.517

12.673

1.00

134.03

A

C

ATOM

752

NZ

LYS

A

97

−33.160

−44.923

12.769

1.00

134.53

A

N

ATOM

753

C

LYS

A

97

−37.447

−41.730

9.442

1.00

131.10

A

C

ATOM

754

O

LYS

A

97

−37.441

−42.878

8.971

1.00

131.23

A

O

ATOM

755

N

LEU

A

98

−37.160

−40.640

8.730

1.00

129.70

A

N

ATOM

756

CA

LEU

A

98

−37.130

−40.642

7.264

1.00

128.31

A

C

ATOM

757

CB

LEU

A

98

−37.201

−39.203

6.736

1.00

128.51

A

C

ATOM

758

CG

LEU

A

98

−38.009

−38.800

5.489

1.00

128.67

A

C

ATOM

759

CD1

LEU

A

98

−37.679

−39.617

4.235

1.00

128.21

A

C

ATOM

760

CD2

LEU

A

98

−39.521

−38.801

5.776

1.00

128.98

A

C

ATOM

761

C

LEU

A

98

−35.917

−41.353

6.668

1.00

127.13

A

C

ATOM

762

O

LEU

A

98

−36.054

−42.206

5.799

1.00

127.18

A

O

ATOM

763

N

ASN

A

99

−34.736

−41.010

7.157

1.00

125.50

A

N

ATOM

764

CA

ASN

A

99

−33.486

−41.373

6.501

1.00

124.11

A

C

ATOM

765

CB

ASN

A

99

−32.443

−40.270

6.777

1.00

124.45

A

C

ATOM

766

CG

ASN

A

99

−33.089

−38.895

7.120

1.00

125.14

A

C

ATOM

767

OD1

ASN

A

99

−32.575

−38.141

7.962

1.00

125.15

A

O

ATOM

768

ND2

ASN

A

99

−34.213

−38.579

6.469

1.00

125.28

A

N

ATOM

769

C

ASN

A

99

−32.964

−42.778

6.891

1.00

122.87

A

C

ATOM

770

O

ASN

A

99

−31.777

−42.954

7.191

1.00

122.66

A

O

ATOM

771

N

THR

A

100

−33.861

−43.768

6.864

1.00

121.29

A

N

ATOM

772

CA

THR

A

100

−33.572

−45.151

7.299

1.00

119.54

A

C

ATOM

773

CB

THR

A

100

−34.764

−45.792

8.075

1.00

119.58

A

C

ATOM

774

OG1

THR

A

100

−35.989

−45.108

7.771

1.00

119.45

A

O

ATOM

775

CG2

THR

A

100

−34.513

−45.751

9.567

1.00

119.76

A

C

ATOM

776

C

THR

A

100

−33.170

−46.148

6.205

1.00

118.22

A

C

ATOM

777

O

THR

A

100

−33.301

−45.888

5.010

1.00

118.24

A

O

ATOM

778

N

ARG

A

101

−32.668

−47.292

6.654

1.00

116.43

A

N

ATOM

779

CA

ARG

A

101

−32.426

−48.447

5.811

1.00

114.67

A

C

ATOM

780

CB

ARG

A

101

−31.170

−49.191

6.286

1.00

114.86

A

C

ATOM

781

CG

ARG

A

101

−30.006

−49.182

5.293

1.00

115.67

A

C

ATOM

782

CD

ARG

A

101

−28.679

−49.571

5.947

1.00

117.54

A

C

ATOM

783

NE

ARG

A

101

−27.978

−48.388

6.455

1.00

119.64

A

N

ATOM

784

CZ

ARG

A

101

−26.864

−47.875

5.933

1.00

120.21

A

C

ATOM

785

NH1

ARG

A

101

−26.284

−48.450

4.886

1.00

121.18

A

N

ATOM

786

NH2

ARG

A

101

−26.320

−46.786

6.465

1.00

120.14

A

N

ATOM

787

C

ARG

A

101

−33.651

−49.363

5.878

1.00

113.12

A

C

ATOM

788

O

ARG

A

101

−34.383

−49.354

6.878

1.00

113.26

A

O

ATOM

789

N

PRO

A

102

−33.892

−50.152

4.813

1.00

111.37

A

N

ATOM

790

CA

PRO

A

102

−35.006

−51.089

4.851

1.00

110.03

A

C

ATOM

791

CB

PRO

A

102

−34.992

−51.702

3.445

1.00

109.91

A

C

ATOM

792

CG

PRO

A

102

−34.236

−50.756

2.620

1.00

110.25

A

C

ATOM

793

CD

PRO

A

102

−33.206

−50.187

3.511

1.00

111.07

A

C

ATOM

794

C

PRO

A

102

−34.790

−52.188

5.880

1.00

108.68

A

C

ATOM

795

O

PRO

A

102

−33.662

−52.521

6.201

1.00

108.59

A

O

ATOM

796

N

SER

A

103

−35.869

−52.751

6.394

1.00

107.44

A

N

ATOM

797

CA

SER

A

103

−35.766

−53.992

7.124

1.00

106.19

A

C

ATOM

798

CB

SER

A

103

−37.127

−54.413

7.655

1.00

106.13

A

C

ATOM

799

OG

SER

A

103

−37.917

−54.955

6.621

1.00

105.32

A

O

ATOM

800

C

SER

A

103

−35.284

−54.985

6.092

1.00

105.65

A

C

ATOM

801

O

SER

A

103

−35.193

−54.641

4.917

1.00

105.94

A

O

ATOM

802

N

THR

A

104

−34.964

−56.208

6.505

1.00

104.80

A

N

ATOM

803

CA

THR

A

104

−34.550

−57.217

5.540

1.00

103.43

A

C

ATOM

804

CB

THR

A

104

−33.938

−58.449

6.212

1.00

103.59

A

C

ATOM

805

OG1

THR

A

104

−32.761

−58.050

6.927

1.00

103.63

A

O

ATOM

806

CG2

THR

A

104

−33.562

−59.508

5.165

1.00

103.73

A

C

ATOM

807

C

THR

A

104

−35.758

−57.576

4.707

1.00

102.27

A

C

ATOM

808

O

THR

A

104

−35.766

−57.361

3.498

1.00

102.12

A

O

ATOM

809

N

GLY

A

105

−36.796

−58.055

5.380

1.00

101.17

A

N

ATOM

810

CA

GLY

A

105

−38.044

−58.457

4.731

1.00

100.14

A

C

ATOM

811

C

GLY

A

105

−38.594

−57.528

3.658

1.00

99.09

A

C

ATOM

812

O

GLY

A

105

−39.199

−57.986

2.684

1.00

98.91

A

O

ATOM

813

N

LEU

A

106

−38.390

−56.226

3.848

1.00

98.09

A

N

ATOM

814

CA

LEU

A

106

−38.909

−55.211

2.945

1.00

97.14

A

C

ATOM

815

CB

LEU

A

106

−39.000

−53.844

3.646

1.00

97.05

A

C

ATOM

816

CG

LEU

A

106

−38.844

−52.519

2.879

1.00

96.66

A

C

ATOM

817

CD1

LEU

A

106

−39.996

−52.247

1.904

1.00

96.43

A

C

ATOM

818

CD2

LEU

A

106

−38.709

−51.372

3.854

1.00

95.77

A

C

ATOM

819

C

LEU

A

106

−38.023

−55.133

1.729

1.00

96.62

A

C

ATOM

820

O

LEU

A

106

−38.520

−55.042

0.610

1.00

96.72

A

O

ATOM

821

N

LEU

A

107

−36.713

−55.168

1.946

1.00

95.85

A

N

ATOM

822

CA

LEU

A

107

−35.786

−55.095

0.837

1.00

95.18

A

C

ATOM

823

CB

LEU

A

107

−34.334

−55.050

1.304

1.00

94.92

A

C

ATOM

824

CG

LEU

A

107

−33.319

−54.998

0.153

1.00

93.56

A

C

ATOM

825

CD1

LEU

A

107

−33.530

−53.763

−0.687

1.00

92.18

A

C

ATOM

826

CD2

LEU

A

107

−31.889

−55.072

0.649

1.00

92.76

A

C

ATOM

827

C

LEU

A

107

−36.000

−56.253

−0.129

1.00

95.10

A

C

ATOM

828

O

LEU

A

107

−35.792

−56.100

−1.326

1.00

95.33

A

O

ATOM

829

N

ARG

A

108

−36.426

−57.403

0.376

1.00

94.70

A

N

ATOM

830

CA

ARG

A

108

−36.740

−58.505

−0.516

1.00

94.78

A

C

ATOM

831

CB

ARG

A

108

−37.256

−59.716

0.263

1.00

95.07

A

C

ATOM

832

CG

ARG

A

108

−37.494

−60.979

−0.585

1.00

97.30

A

C

ATOM

833

CD

ARG

A

108

−37.690

−62.256

0.270

1.00

101.92

A

C

ATOM

834

NE

ARG

A

108

−38.029

−61.996

1.676

1.00

106.59

A

N

ATOM

835

CZ

ARG

A

108

−39.155

−61.414

2.117

1.00

110.59

A

C

ATOM

836

NH1

ARG

A

108

−39.337

−61.240

3.425

1.00

112.80

A

N

ATOM

837

NH2

ARG

A

108

−40.102

−60.987

1.274

1.00

111.51

A

N

ATOM

838

C

ARG

A

108

−37.762

−58.010

−1.532

1.00

94.14

A

C

ATOM

839

O

ARG

A

108

−37.521

−58.021

−2.744

1.00

94.26

A

O

ATOM

840

N

HIS

A

109

−38.882

−57.530

−1.012

1.00

93.50

A

N

ATOM

841

CA

HIS

A

109

−39.964

−56.987

−1.820

1.00

92.75

A

C

ATOM

842

CB

HIS

A

109

−41.027

−56.395

−0.897

1.00

92.37

A

C

ATOM

843

CG

HIS

A

109

−42.092

−55.621

−1.603

1.00

90.81

A

C

ATOM

844

ND1

HIS

A

109

−43.233

−56.208

−2.100

1.00

89.32

A

N

ATOM

845

CE1

HIS

A

109

−44.002

−55.280

−2.636

1.00

88.92

A

C

ATOM

846

NE2

HIS

A

109

−43.403

−54.111

−2.500

1.00

88.63

A

N

ATOM

847

CD2

HIS

A

109

−42.206

−54.297

−1.860

1.00

89.44

A

C

ATOM

848

C

HIS

A

109

−39.475

−55.941

−2.821

1.00

92.55

A

C

ATOM

849

O

HIS

A

109

−39.790

−56.017

−4.001

1.00

92.58

A

O

ATOM

850

N

ILE

A

110

−38.708

−54.969

−2.345

1.00

92.27

A

N

ATOM

851

CA

ILE

A

110

−38.276

−53.881

−3.199

1.00

91.90

A

C

ATOM

852

CB

ILE

A

110

−37.388

−52.868

−2.466

1.00

91.59

A

C

ATOM

853

CG1

ILE

A

110

−38.168

−52.222

−1.310

1.00

90.96

A

C

ATOM

854

CD1

ILE

A

110

−37.451

−51.090

−0.584

1.00

89.65

A

C

ATOM

855

CG2

ILE

A

110

−36.846

−51.854

−3.465

1.00

90.96

A

C

ATOM

856

C

ILE

A

110

−37.533

−54.446

−4.392

1.00

92.23

A

C

ATOM

857

O

ILE

A

110

−37.935

−54.231

−5.529

1.00

92.92

A

O

ATOM

858

N

LEU

A

111

−36.467

−55.192

−4.136

1.00

92.12

A

N

ATOM

859

CA

LEU

A

111

−35.643

−55.697

−5.217

1.00

91.77

A

C

ATOM

860

CB

LEU

A

111

−34.491

−56.543

−4.677

1.00

91.73

A

C

ATOM

861

CG

LEU

A

111

−33.467

−55.903

−3.741

1.00

90.36

A

C

ATOM

862

CD1

LEU

A

111

−32.463

−56.958

−3.406

1.00

90.12

A

C

ATOM

863

CD2

LEU

A

111

−32.781

−54.692

−4.345

1.00

88.55

A

C

ATOM

864

C

LEU

A

111

−36.502

−56.502

−6.169

1.00

91.90

A

C

ATOM

865

O

LEU

A

111

−36.383

−56.359

−7.378

1.00

91.88

A

O

ATOM

866

N

GLN

A

112

−37.377

−57.333

−5.611

1.00

92.19

A

N

ATOM

867

CA

GLN

A

112

−38.380

−58.057

−6.389

1.00

92.61

A

C

ATOM

868

CB

GLN

A

112

−39.414

−58.680

−5.441

1.00

92.65

A

C

ATOM

869

CG

GLN

A

112

−40.151

−59.873

−5.987

1.00

93.30

A

C

ATOM

870

CD

GLN

A

112

−39.304

−61.111

−5.954

1.00

95.39

A

C

ATOM

871

OE1

GLN

A

112

−38.080

−61.029

−5.840

1.00

96.91

A

O

ATOM

872

NE2

GLN

A

112

−39.939

−62.272

−6.046

1.00

95.38

A

N

ATOM

873

C

GLN

A

112

−39.073

−57.130

−7.413

1.00

92.52

A

C

ATOM

874

O

GLN

A

112

−39.107

−57.420

−8.600

1.00

92.65

A

O

ATOM

875

N

GLN

A

113

−39.600

−56.013

−6.930

1.00

92.38

A

N

ATOM

876

CA

GLN

A

113

−40.245

−55.004

−7.751

1.00

92.42

A

C

ATOM

877

CB

GLN

A

113

−40.604

−53.816

−6.877

1.00

91.83

A

C

ATOM

878

CG

GLN

A

113

−41.894

−53.927

−6.140

1.00

87.77

A

C

ATOM

879

CD

GLN

A

113

−42.411

−52.578

−5.848

1.00

82.89

A

C

ATOM

880

OE1

GLN

A

113

−41.639

−51.658

−5.644

1.00

82.06

A

O

ATOM

881

NE2

GLN

A

113

−43.713

−52.425

−5.856

1.00

81.92

A

N

ATOM

882

C

GLN

A

113

−39.361

−54.474

−8.860

1.00

93.60

A

C

ATOM

883

O

GLN

A

113

−39.792

−54.359

−9.999

1.00

93.71

A

O

ATOM

884

N

VAL

A

114

−38.136

−54.118

−8.494

1.00

95.00

A

N

ATOM

885

CA

VAL

A

114

−37.148

−53.565

−9.417

1.00

96.40

A

C

ATOM

886

CB

VAL

A

114

−35.803

−53.293

−8.696

1.00

96.33

A

C

ATOM

887

CG1

VAL

A

114

−34.789

−52.673

−9.645

1.00

96.52

A

C

ATOM

888

CG2

VAL

A

114

−36.021

−52.384

−7.508

1.00

96.64

A

C

ATOM

889

C

VAL

A

114

−36.922

−54.495

−10.597

1.00

97.20

A

C

ATOM

890

O

VAL

A

114

−36.969

−54.078

−11.742

1.00

97.10

A

O

ATOM

891

N

TYR

A

115

−36.677

−55.758

−10.291

1.00

98.86

A

N

ATOM

892

CA

TYR

A

115

−36.532

−56.801

−11.287

1.00

100.76

A

C

ATOM

893

CB

TYR

A

115

−36.385

−58.127

−10.557

1.00

100.48

A

C

ATOM

894

CG

TYR

A

115

−35.930

−59.319

−11.360

1.00

100.03

A

C

ATOM

895

CD1

TYR

A

115

−34.578

−59.555

−11.591

1.00

100.29

A

C

ATOM

896

CE1

TYR

A

115

−34.154

−60.679

−12.290

1.00

99.90

A

C

ATOM

897

CZ

TYR

A

115

−35.091

−61.589

−12.745

1.00

99.88

A

C

ATOM

898

OH

TYR

A

115

−34.690

−62.708

−13.444

1.00

100.50

A

O

ATOM

899

CE2

TYR

A

115

−36.436

−61.386

−12.504

1.00

99.43

A

C

ATOM

900

CD2

TYR

A

115

−36.844

−60.258

−11.811

1.00

99.36

A

C

ATOM

901

C

TYR

A

115

−37.755

−56.813

−12.218

1.00

102.30

A

C

ATOM

902

O

TYR

A

115

−37.630

−56.563

−13.424

1.00

102.67

A

O

ATOM

903

N

ASN

A

116

−38.935

−57.057

−11.652

1.00

103.84

A

N

ATOM

904

CA

ASN

A

116

−40.159

−57.132

−12.437

1.00

105.35

A

C

ATOM

905

CB

ASN

A

116

−41.409

−57.186

−11.544

1.00

105.53

A

C

ATOM

906

CG

ASN

A

116

−41.299

−58.201

−10.395

1.00

106.42

A

C

ATOM

907

OD1

ASN

A

116

−41.958

−58.039

−9.362

1.00

107.61

A

O

ATOM

908

ND2

ASN

A

116

−40.473

−59.236

−10.563

1.00

105.87

A

N

ATOM

909

C

ASN

A

116

−40.259

−55.963

−13.411

1.00

106.26

A

C

ATOM

910

O

ASN

A

116

−40.374

−56.166

−14.612

1.00

106.58

A

O

ATOM

911

N

HIS

A

117

−40.184

−54.742

−12.899

1.00

107.58

A

N

ATOM

912

CA

HIS

A

117

−40.309

−53.569

−13.753

1.00

109.13

A

C

ATOM

913

CB

HIS

A

117

−40.525

−52.295

−12.932

1.00

108.80

A

C

ATOM

914

CG

HIS

A

117

−41.802

−52.277

−12.155

1.00

108.67

A

C

ATOM

915

ND1

HIS

A

117

−43.040

−52.297

−12.757

1.00

107.97

A

N

ATOM

916

CE1

HIS

A

117

−43.979

−52.264

−11.827

1.00

107.76

A

C

ATOM

917

NE2

HIS

A

117

−43.394

−52.216

−10.645

1.00

107.59

A

N

ATOM

918

CD2

HIS

A

117

−42.033

−52.221

−10.821

1.00

108.97

A

C

ATOM

919

C

HIS

A

117

−39.108

−53.374

−14.674

1.00

110.51

A

C

ATOM

920

O

HIS

A

117

−39.188

−52.593

−15.617

1.00

110.72

A

O

ATOM

921

N

SER

A

118

−38.002

−54.067

−14.412

1.00

112.27

A

N

ATOM

922

CA

SER

A

118

−36.784

−53.842

−15.193

1.00

114.20

A

C

ATOM

923

CB

SER

A

118

−35.614

−53.463

−14.292

1.00

114.06

A

C

ATOM

924

OG

SER

A

118

−35.922

−52.302

−13.543

1.00

113.94

A

O

ATOM

925

C

SER

A

118

−36.410

−55.003

−16.100

1.00

115.70

A

C

ATOM

926

O

SER

A

118

−36.144

−54.806

−17.286

1.00

115.72

A

O

ATOM

927

N

VAL

A

119

−36.383

−56.208

−15.544

1.00

117.78

N

ATOM

928

CA

VAL

A

119

−36.160

−57.408

−16.340

1.00

119.93

C

ATOM

929

CB

VAL

A

119

−35.673

−58.596

−15.477

1.00

119.63

C

ATOM

930

CG1

VAL

A

119

−35.786

−59.905

−16.231

1.00

119.45

C

ATOM

931

CG2

VAL

A

119

−34.234

−58.376

−15.052

1.00

119.70

C

ATOM

932

C

VAL

A

119

−37.459

−57.724

−17.065

1.00

121.78

C

ATOM

933

O

VAL

A

119

−38.297

−58.483

−16.566

1.00

122.10

O

ATOM

934

N

THR

A

120

−37.623

−57.105

−18.234

1.00

124.15

N

ATOM

935

CA

THR

A

120

−38.833

−57.259

−19.053

1.00

126.32

C

ATOM

936

CB

THR

A

120

−38.907

−56.229

−20.231

1.00

126.35

C

ATOM

937

OG1

THR

A

120

−37.839

−56.462

−21.161

1.00

127.01

O

ATOM

938

CG2

THR

A

120

−38.827

−54.783

−19.725

1.00

126.37

C

ATOM

939

C

THR

A

120

−38.957

−58.675

−19.605

1.00

127.69

C

ATOM

940

O

THR

A

120

−40.058

−59.198

−19.699

1.00

128.05

O

ATOM

941

N

ASP

A

121

−37.830

−59.299

−19.945

1.00

129.56

N

ATOM

942

CA

ASP

A

121

−37.846

−60.622

−20.563

1.00

131.49

C

ATOM

943

CB

ASP

A

121

−37.269

−60.545

−21.982

1.00

131.52

C

ATOM

944

CG

ASP

A

121

−37.878

−61.574

−22.925

1.00

131.55

C

ATOM

945

OD1

ASP

A

121

−38.153

−62.721

−22.491

1.00

130.99

O

ATOM

946

OD2

ASP

A

121

−38.068

−61.227

−24.111

1.00

131.26

O

ATOM

947

C

ASP

A

121

−37.104

−61.664

−19.723

1.00

132.90

C

ATOM

948

O

ASP

A

121

−35.930

−61.933

−19.971

1.00

132.87

O

ATOM

949

N

PRO

A

122

−37.801

−62.273

−18.743

1.00

134.59

N

ATOM

950

CA

PRO

A

122

−37.178

−63.129

−17.722

1.00

136.07

C

ATOM

951

CB

PRO

A

122

−38.356

−63.509

−16.815

1.00

135.91

C

ATOM

952

CG

PRO

A

122

−39.542

−63.437

−17.700

1.00

135.41

C

ATOM

953

CD

PRO

A

122

−39.271

−62.272

−18.621

1.00

134.73

C

ATOM

954

C

PRO

A

122

−36.526

−64.390

−18.279

1.00

137.66

C

ATOM

955

O

PRO

A

122

−35.513

−64.845

−17.742

1.00

137.77

O

ATOM

956

N

GLU

A

123

−37.114

−64.941

−19.340

1.00

139.58

N

ATOM

957

CA

GLU

A

123

−36.647

−66.184

−19.943

1.00

141.45

C

ATOM

958

CB

GLU

A

123

−37.787

−66.856

−20.720

1.00

141.28

C

ATOM

959

CG

GLU

A

123

−37.550

−68.326

−21.086

1.00

141.34

C

ATOM

960

CD

GLU

A

123

−37.023

−69.163

−19.927

1.00

141.02

C

ATOM

961

OE1

GLU

A

123

−35.964

−69.805

−20.088

1.00

140.73

O

ATOM

962

OE2

GLU

A

123

−37.659

−69.179

−18.856

1.00

141.54

O

ATOM

963

C

GLU

A

123

−35.437

−65.934

−20.841

1.00

142.98

C

ATOM

964

O

GLU

A

123

−34.639

−66.844

−21.088

1.00

143.13

O

ATOM

965

N

LYS

A

124

−35.297

−64.690

−21.299

1.00

144.91

N

ATOM

966

CA

LYS

A

124

−34.191

−64.272

−22.165

1.00

146.91

C

ATOM

967

CB

LYS

A

124

−34.550

−62.953

−22.837

1.00

146.74

C

ATOM

968

CG

LYS

A

124

−35.060

−63.102

−24.255

1.00

146.47

C

ATOM

969

CD

LYS

A

124

−34.116

−62.423

−25.217

1.00

145.90

C

ATOM

970

CE

LYS

A

124

−34.296

−60.917

−25.162

1.00

145.62

C

ATOM

971

NZ

LYS

A

124

−33.048

−60.206

−25.518

1.00

145.62

N

ATOM

972

C

LYS

A

124

−32.822

−64.170

−21.468

1.00

148.55

C

ATOM

973

O

LYS

A

124

−31.928

−63.451

−21.932

1.00

148.68

O

ATOM

974

N

LEU

A

125

−32.671

−64.895

−20.362

1.00

150.70

N

ATOM

975

CA

LEU

A

125

−31.401

−65.007

−19.649

1.00

152.83

C

ATOM

976

CB

LEU

A

125

−31.524

−64.444

−18.226

1.00

152.70

C

ATOM

977

CG

LEU

A

125

−31.804

−62.947

−18.024

1.00

152.49

C

ATOM

978

CD1

LEU

A

125

−32.110

−62.651

−16.565

1.00

152.28

C

ATOM

979

CD2

LEU

A

125

−30.650

−62.084

−18.503

1.00

152.11

C

ATOM

980

C

LEU

A

125

−30.937

−66.467

−19.622

1.00

154.52

C

ATOM

981

O

LEU

A

125

−30.066

−66.848

−18.834

1.00

154.82

O

ATOM

982

N

ASN

A

126

−31.550

−67.282

−20.479

1.00

156.62

N

ATOM

983

CA

ASN

A

126

−31.116

−68.658

−20.734

1.00

158.65

C

ATOM

984

CB

ASN

A

126

−31.977

−69.663

−19.957

1.00

158.64

C

ATOM

985

CG

ASN

A

126

−31.550

−69.804

−18.503

1.00

158.89

C

ATOM

986

OD1

ASN

A

126

−31.014

−70.840

−18.100

1.00

158.95

O

ATOM

987

ND2

ASN

A

126

−31.789

−68.764

−17.708

1.00

158.90

N

ATOM

988

C

ASN

A

126

−31.138

−68.962

−22.239

1.00

160.04

C

ATOM

989

O

ASN

A

126

−31.161

−70.123

−22.660

1.00

160.17

O

ATOM

990

N

ASN

A

127

−31.134

−67.893

−23.036

1.00

161.88

N

ATOM

991

CA

ASN

A

127

−31.115

−67.972

−24.497

1.00

163.62

C

ATOM

992

CB

ASN

A

127

−32.304

−67.207

−25.093

1.00

163.57

C

ATOM

993

CG

ASN

A

127

−33.318

−68.118

−25.768

1.00

163.96

C

ATOM

994

OD1

ASN

A

127

−33.038

−69.287

−26.059

1.00

164.21

O

ATOM

995

ND2

ASN

A

127

−34.504

−67.577

−26.038

1.00

163.90

N

ATOM

996

C

ASN

A

127

−29.820

−67.454

−25.119

1.00

164.83

C

ATOM

997

O

ASN

A

127

−29.559

−67.707

−26.299

1.00

164.96

O

ATOM

998

N

TYR

A

128

−29.025

−66.725

−24.329

1.00

166.43

N

ATOM

999

CA

TYR

A

128

−27.774

−66.111

−24.806

1.00

167.84

C

ATOM

1000

CB

TYR

A

128

−27.170

−65.122

−23.769

1.00

167.86

C

ATOM

1001

CG

TYR

A

128

−27.131

−65.552

−22.298

1.00

167.90

C

ATOM

1002

CD1

TYR

A

128

−26.892

−66.881

−21.923

1.00

167.91

C

ATOM

1003

CE1

TYR

A

128

−26.841

−67.262

−20.582

1.00

168.14

C

ATOM

1004

CZ

TYR

A

128

−27.010

−66.309

−19.594

1.00

168.45

C

ATOM

1005

OH

TYR

A

128

−26.957

−66.686

−18.268

1.00

168.38

O

ATOM

1006

CE2

TYR

A

128

−27.235

−64.979

−19.935

1.00

168.53

C

ATOM

1007

CD2

TYR

A

128

−27.286

−64.608

−21.282

1.00

167.98

C

ATOM

1008

C

TYR

A

128

−26.750

−67.158

−25.265

1.00

168.74

C

ATOM

1009

O

TYR

A

128

−26.914

−67.784

−26.315

1.00

168.84

O

ATOM

1010

N

GLU

A

129

−25.687

−67.322

−24.489

1.00

169.93

N

ATOM

1011

CA

GLU

A

129

−24.806

−68.468

−24.627

1.00

171.09

C

ATOM

1012

CB

GLU

A

129

−23.470

−68.049

−25.254

1.00

171.03

C

ATOM

1013

CG

GLU

A

129

−23.566

−67.808

−26.768

1.00

171.17

C

ATOM

1014

CD

GLU

A

129

−22.213

−67.721

−27.464

1.00

171.32

C

ATOM

1015

OE1

GLU

A

129

−21.966

−68.548

−28.370

1.00

171.27

O

ATOM

1016

OE2

GLU

A

129

−21.402

−66.831

−27.118

1.00

171.14

O

ATOM

1017

C

GLU

A

129

−24.660

−69.124

−23.240

1.00

171.92

C

ATOM

1018

O

GLU

A

129

−23.680

−68.863

−22.531

1.00

172.00

O

ATOM

1019

N

PRO

A

130

−25.660

−69.957

−22.840

1.00

172.71

N

ATOM

1020

CA

PRO

A

130

−25.750

−70.540

−21.491

1.00

173.17

C

ATOM

1021

CB

PRO

A

130

−27.222

−70.985

−21.381

1.00

173.16

C

ATOM

1022

CG

PRO

A

130

−27.883

−70.567

−22.679

1.00

173.07

C

ATOM

1023

CD

PRO

A

130

−26.785

−70.409

−23.679

1.00

172.78

C

ATOM

1024

C

PRO

A

130

−24.792

−71.718

−21.300

1.00

173.69

C

ATOM

1025

O

PRO

A

130

−25.213

−72.887

−21.242

1.00

173.66

O

ATOM

1026

N

PHE

A

131

−23.506

−71.366

−21.206

1.00

174.28

N

ATOM

1027

CA

PHE

A

131

−22.381

−72.287

−21.015

1.00

174.71

C

ATOM

1028

CB

PHE

A

131

−22.248

−73.261

−22.206

1.00

174.70

C

ATOM

1029

CG

PHE

A

131

−21.764

−74.649

−21.834

1.00

174.86

C

ATOM

1030

CD1

PHE

A

131

−22.304

−75.336

−20.744

1.00

174.99

C

ATOM

1031

CE1

PHE

A

131

−21.858

−76.617

−20.417

1.00

174.83

C

ATOM

1032

CZ

PHE

A

131

−20.879

−77.229

−21.195

1.00

174.69

C

ATOM

1033

CE2

PHE

A

131

−20.341

−76.562

−22.287

1.00

174.58

C

ATOM

1034

CD2

PHE

A

131

−20.793

−75.287

−22.608

1.00

174.75

C

ATOM

1035

C

PHE

A

131

−21.119

−71.416

−20.832

1.00

174.86

C

ATOM

1036

O

PHE

A

131

−20.247

−71.743

−20.023

1.00

175.08

O

ATOM

1037

N

SER

A

132

−21.061

−70.294

−21.558

1.00

174.97

N

ATOM

1038

CA

SER

A

132

−19.960

−69.310

−21.489

1.00

175.00

C

ATOM

1039

CB

SER

A

132

−19.937

−68.461

−22.772

1.00

174.99

C

ATOM

1040

OG

SER

A

132

−19.127

−67.304

−22.638

1.00

174.53

O

ATOM

1041

C

SER

A

132

−20.034

−68.385

−20.255

1.00

175.05

C

ATOM

1042

O

SER

A

132

−21.132

−67.979

−19.852

1.00

174.99

O

ATOM

1043

N

PRO

A

133

−18.863

−68.047

−19.659

1.00

175.04

N

ATOM

1044

CA

PRO

A

133

−18.789

−67.099

−18.536

1.00

175.00

C

ATOM

1045

CB

PRO

A

133

−17.290

−67.060

−18.211

1.00

174.97

C

ATOM

1046

CG

PRO

A

133

−16.776

−68.373

−18.673

1.00

175.04

C

ATOM

1047

CD

PRO

A

133

−17.548

−68.660

−19.930

1.00

175.02

C

ATOM

1048

C

PRO

A

133

−19.277

−65.695

−18.902

1.00

174.94

C

ATOM

1049

O

PRO

A

133

−20.354

−65.277

−18.465

1.00

174.78

O

ATOM

1050

N

GLU

A

138

−29.909

−69.344

−11.491

1.00

122.62

N

ATOM

1051

CA

GLU

A

138

−30.959

−69.003

−10.522

1.00

122.35

C

ATOM

1052

CB

GLU

A

138

−32.087

−70.054

−10.528

1.00

122.42

C

ATOM

1053

CG

GLU

A

138

−33.396

−69.606

−9.847

1.00

122.39

C

ATOM

1054

CD

GLU

A

138

−33.888

−68.247

−10.321

1.00

122.02

C

ATOM

1055

OE1

GLU

A

138

−33.217

−67.228

−10.045

1.00

121.61

O

ATOM

1056

OE2

GLU

A

138

−34.955

−68.197

−10.964

1.00

122.23

O

ATOM

1057

C

GLU

A

138

−30.424

−68.752

−9.098

1.00

121.95

C

ATOM

1058

O

GLU

A

138

−29.910

−69.663

−8.432

1.00

121.97

O

ATOM

1059

N

THR

A

139

−30.569

−67.503

−8.654

1.00

121.28

A

N

ATOM

1060

CA

THR

A

139

−29.998

−67.012

−7.393

1.00

120.63

A

C

ATOM

1061

CB

THR

A

139

−28.869

−65.948

−7.657

1.00

120.86

A

C

ATOM

1062

OG1

THR

A

139

−27.709

−66.586

−8.219

1.00

121.04

A

O

ATOM

1063

CG2

THR

A

139

−28.463

−65.223

−6.371

1.00

121.28

A

C

ATOM

1064

C

THR

A

139

−31.088

−66.414

−6.493

1.00

119.61

A

C

ATOM

1065

O

THR

A

139

−32.022

−65.767

−6.977

1.00

119.72

A

O

ATOM

1066

N

SER

A

140

−30.965

−66.629

−5.186

1.00

118.16

A

N

ATOM

1067

CA

SER

A

140

−31.941

−66.087

−4.255

1.00

116.53

A

C

ATOM

1068

CB

SER

A

140

−32.513

−67.165

−3.342

1.00

116.83

A

C

ATOM

1069

OG

SER

A

140

−33.619

−66.633

−2.637

1.00

117.73

A

O

ATOM

1070

C

SER

A

140

−31.398

−64.956

−3.418

1.00

115.04

A

C

ATOM

1071

O

SER

A

140

−30.184

−64.747

−3.326

1.00

114.61

A

O

ATOM

1072

N

PHE

A

141

−32.341

−64.232

−2.825

1.00

113.32

A

N

ATOM

1073

CA

PHE

A

141

−32.081

−63.082

−1.976

1.00

111.77

A

C

ATOM

1074

CB

PHE

A

141

−33.333

−62.202

−1.952

1.00

111.32

A

C

ATOM

1075

CG

PHE

A

141

−33.353

−61.197

−0.857

1.00

109.82

A

C

ATOM

1076

CD1

PHE

A

141

−32.867

−59.922

−1.067

1.00

108.92

A

C

ATOM

1077

CE1

PHE

A

141

−32.887

−58.980

−0.051

1.00

108.69

A

C

ATOM

1078

CZ

PHE

A

141

−33.409

−59.311

1.193

1.00

108.97

A

C

ATOM

1079

CE2

PHE

A

141

−33.908

−60.580

1.414

1.00

109.04

A

C

ATOM

1080

CD2

PHE

A

141

−33.882

−61.516

0.385

1.00

109.44

A

C

ATOM

1081

C

PHE

A

141

−31.727

−63.579

−0.580

1.00

111.19

A

C

ATOM

1082

O

PHE

A

141

−30.793

−63.083

0.056

1.00

110.99

A

O

ATOM

1083

N

ASP

A

142

−32.488

−64.568

−0.120

1.00

110.29

A

N

ATOM

1084

CA

ASP

A

142

−32.258

−65.219

1.157

1.00

109.27

A

C

ATOM

1085

CB

ASP

A

142

−33.087

−66.500

1.247

1.00

109.11

A

C

ATOM

1086

CG

ASP

A

142

−34.535

−66.289

0.833

1.00

108.30

A

C

ATOM

1087

OD1

ASP

A

142

−35.038

−65.152

0.964

1.00

107.42

A

O

ATOM

1088

OD2

ASP

A

142

−35.167

−67.262

0.372

1.00

107.28

A

O

ATOM

1089

C

ASP

A

142

−30.781

−65.529

1.311

1.00

108.81

A

C

ATOM

1090

O

ASP

A

142

−30.120

−64.967

2.183

1.00

109.14

A

O

ATOM

1091

N

LEU

A

143

−30.265

−66.392

0.437

1.00

107.87

A

N

ATOM

1092

CA

LEU

A

143

−28.848

−66.771

0.440

1.00

106.92

A

C

ATOM

1093

CB

LEU

A

143

−28.483

−67.450

−0.883

1.00

106.94

A

C

ATOM

1094

CG

LEU

A

143

−27.239

−68.336

−0.972

1.00

106.72

A

C

ATOM

1095

CD1

LEU

A

143

−27.518

−69.493

−1.900

1.00

107.28

A

C

ATOM

1096

CD2

LEU

A

143

−26.021

−67.576

−1.452

1.00

106.57

A

C

ATOM

1097

C

LEU

A

143

−27.941

−65.576

0.680

1.00

106.27

A

C

ATOM

1098

O

LEU

A

143

−27.200

−65.550

1.646

1.00

106.11

A

O

ATOM

1099

N

VAL

A

144

−28.031

−64.586

−0.198

1.00

105.85

A

N

ATOM

1100

CA

VAL

A

144

−27.158

−63.419

−0.163

1.00

105.76

A

C

ATOM

1101

CB

VAL

A

144

−27.533

−62.401

−1.262

1.00

105.92

A

C

ATOM

1102

CG1

VAL

A

144

−26.543

−61.238

−1.290

1.00

105.32

A

C

ATOM

1103

CG2

VAL

A

144

−27.600

−63.085

−2.624

1.00

106.23

A

C

ATOM

1104

C

VAL

A

144

−27.207

−62.733

1.191

1.00

105.69

A

C

ATOM

1105

O

VAL

A

144

−26.166

−62.436

1.774

1.00

105.77

A

O

ATOM

1106

N

ALA

A

145

−28.423

−62.493

1.684

1.00

105.53

A

N

ATOM

1107

CA

ALA

A

145

−28.627

−61.930

3.013

1.00

104.91

A

C

ATOM

1108

CB

ALA

A

145

−30.070

−62.066

3.439

1.00

104.87

A

C

ATOM

1109

C

ALA

A

145

−27.720

−62.646

3.988

1.00

104.65

A

C

ATOM

1110

O

ALA

A

145

−26.987

−62.000

4.721

1.00

104.81

A

O

ATOM

1111

N

GLN

A

146

−27.738

−63.978

3.965

1.00

104.22

A

N

ATOM

1112

CA

GLN

A

146

−26.919

−64.759

4.876

1.00

103.95

A

C

ATOM

1113

CB

GLN

A

146

−27.111

−66.251

4.658

1.00

103.98

A

C

ATOM

1114

CG

GLN

A

146

−26.538

−67.077

5.793

1.00

104.95

A

C

ATOM

1115

CD

GLN

A

146

−26.068

−68.461

5.367

1.00

106.24

A

C

ATOM

1116

OE1

GLN

A

146

−25.018

−68.931

5.823

1.00

105.97

A

O

ATOM

1117

NE2

GLN

A

146

−26.838

−69.123

4.493

1.00

106.07

A

N

ATOM

1118

C

GLN

A

146

−25.456

−64.411

4.729

1.00

103.76

A

C

ATOM

1119

O

GLN

A

146

−24.802

−64.069

5.704

1.00

104.00

A

O

ATOM

1120

N

MET

A

147

−24.954

−64.471

3.501

1.00

103.72

A

N

ATOM

1121

CA

MET

A

147

−23.542

−64.220

3.223

1.00

103.38

A

C

ATOM

1122

CB

MET

A

147

−23.209

−64.601

1.786

1.00

102.77

A

C

ATOM

1123

CG

MET

A

147

−23.824

−65.898

1.341

1.00

101.47

A

C

ATOM

1124

SD

MET

A

147

−23.047

−67.340

2.084

1.00

100.07

A

S

ATOM

1125

CE

MET

A

147

−24.302

−68.599

1.868

1.00

98.57

A

C

ATOM

1126

C

MET

A

147

−23.195

−62.762

3.477

1.00

103.90

A

C

ATOM

1127

O

MET

A

147

−22.086

−62.329

3.214

1.00

103.84

A

O

ATOM

1128

N

ILE

A

148

−24.166

−62.008

3.973

1.00

104.56

A

N

ATOM

1129

CA

ILE

A

148

−23.946

−60.638

4.389

1.00

105.39

A

C

ATOM

1130

CB

ILE

A

148

−25.110

−59.733

3.944

1.00

105.31

A

C

ATOM

1131

CG1

ILE

A

148

−24.993

−59.418

2.455

1.00

104.87

A

C

ATOM

1132

CD1

ILE

A

148

−26.317

−59.129

1.812

1.00

105.02

A

C

ATOM

1133

CG2

ILE

A

148

−25.179

−58.450

4.782

1.00

104.85

A

C

ATOM

1134

C

ILE

A

148

−23.841

−60.624

5.902

1.00

106.30

A

C

ATOM

1135

O

ILE

A

148

−23.096

−59.819

6.473

1.00

106.42

A

O

ATOM

1136

N

ASP

A

149

−24.593

−61.524

6.537

1.00

107.27

A

N

ATOM

1137

CA

ASP

A

149

−24.664

−61.604

7.988

1.00

108.31

A

C

ATOM

1138

CB

ASP

A

149

−25.669

−62.666

8.418

1.00

108.25

A

C

ATOM

1139

CG

ASP

A

149

−27.095

−62.283

8.103

1.00

109.02

A

C

ATOM

1140

OD1

ASP

A

149

−27.366

−61.070

7.944

1.00

110.17

A

O

ATOM

1141

OD2

ASP

A

149

−27.953

−63.196

8.023

1.00

109.04

A

O

ATOM

1142

C

ASP

A

149

−23.302

−61.926

8.558

1.00

109.13

A

C

ATOM

1143

O

ASP

A

149

−22.696

−61.094

9.227

1.00

109.38

A

O

ATOM

1144

N

GLU

A

150

−22.811

−63.126

8.272

1.00

110.18

A

N

ATOM

1145

CA

GLU

A

150

−21.523

−63.552

8.796

1.00

111.36

A

C

ATOM

1146

CB

GLU

A

150

−21.227

−65.003

8.437

1.00

111.58

A

C

ATOM

1147

CG

GLU

A

150

−22.168

−65.999

9.074

1.00

113.22

A

C

ATOM

1148

CD

GLU

A

150

−22.105

−67.345

8.388

1.00

115.56

A

C

ATOM

1149

OE1

GLU

A

150

−21.987

−67.353

7.139

1.00

116.52

A

O

ATOM

1150

OE2

GLU

A

150

−22.168

−68.384

9.091

1.00

115.98

A

O

ATOM

1151

C

GLU

A

150

−20.415

−62.640

8.291

1.00

111.65

A

C

ATOM

1152

O

GLU

A

150

−19.692

−62.056

9.094

1.00

112.09

A

O

ATOM

1153

N

ILE

A

151

−20.300

−62.499

6.970

1.00

111.73

A

N

ATOM

1154

CA

ILE

A

151

−19.300

−61.621

6.367

1.00

111.70

A

C

ATOM

1155

CB

ILE

A

151

−19.724

−61.186

4.944

1.00

111.67

A

C

ATOM

1156

CG1

ILE

A

151

−19.205

−62.196

3.923

1.00

111.68

A

C

ATOM

1157

CD1

ILE

A

151

−17.729

−62.111

3.647

1.00

112.17

A

C

ATOM

1158

CG2

ILE

A

151

−19.247

−59.773

4.593

1.00

111.38

A

C

ATOM

1159

C

ILE

A

151

−18.991

−60.417

7.254

1.00

111.89

A

C

ATOM

1160

O

ILE

A

151

−17.823

−60.047

7.430

1.00

111.96

A

O

ATOM

1161

N

LYS

A

152

−20.042

−59.840

7.831

1.00

111.95

A

N

ATOM

1162

CA

LYS

A

152

−19.924

−58.696

8.718

1.00

112.37

A

C

ATOM

1163

CB

LYS

A

152

−19.314

−59.121

10.062

1.00

112.43

A

C

ATOM

1164

CG

LYS

A

152

−19.600

−58.167

11.223

1.00

113.91

A

C

ATOM

1165

CD

LYS

A

152

−18.364

−57.331

11.600

1.00

115.98

A

C

ATOM

1166

CE

LYS

A

152

−18.348

−55.950

10.945

1.00

116.28

A

C

ATOM

1167

NZ

LYS

A

152

−19.371

−55.033

11.524

1.00

117.21

A

N

ATOM

1168

C

LYS

A

152

−19.133

−57.569

8.044

1.00

112.21

A

C

ATOM

1169

O

LYS

A

152

−17.934

−57.687

7.794

1.00

112.05

A

O

ATOM

1170

N

MET

A

153

−19.816

−56.474

7.745

1.00

112.28

A

N

ATOM

1171

CA

MET

A

153

−19.178

−55.393

7.024

1.00

112.54

A

C

ATOM

1172

CB

MET

A

153

−19.952

−55.044

5.760

1.00

112.47

A

C

ATOM

1173

CG

MET

A

153

−19.949

−56.139

4.734

1.00

112.04

A

C

ATOM

1174

SD

MET

A

153

−19.755

−55.436

3.109

1.00

111.27

A

S

ATOM

1175

CE

MET

A

153

−20.314

−56.816

2.136

1.00

111.40

A

C

ATOM

1176

C

MET

A

153

−19.025

−54.163

7.873

1.00

112.84

A

C

ATOM

1177

O

MET

A

153

−20.005

−53.474

8.160

1.00

113.02

A

O

ATOM

1178

N

THR

A

154

−17.784

−53.892

8.267

1.00

113.08

A

N

ATOM

1179

CA

THR

A

154

−17.438

−52.658

8.955

1.00

113.22

A

C

ATOM

1180

CB

THR

A

154

−15.972

−52.664

9.421

1.00

113.33

A

C

ATOM

1181

OG1

THR

A

154

−15.102

−52.391

8.311

1.00

113.58

A

O

ATOM

1182

CG2

THR

A

154

−15.605

−54.012

10.038

1.00

113.35

A

C

ATOM

1183

C

THR

A

154

−17.634

−51.511

7.982

1.00

113.29

A

C

ATOM

1184

O

THR

A

154

−17.495

−51.692

6.768

1.00

113.25

A

O

ATOM

1185

N

ASP

A

155

−17.946

−50.333

8.508

1.00

113.44

A

N

ATOM

1186

CA

ASP

A

155

−18.173

−49.157

7.657

1.00

113.63

A

C

ATOM

1187

CB

ASP

A

155

−18.685

−47.946

8.473

1.00

113.84

A

C

ATOM

1188

CG

ASP

A

155

−18.525

−48.123

9.985

1.00

113.84

A

C

ATOM

1189

OD1

ASP

A

155

−19.249

−48.960

10.569

1.00

113.56

A

O

ATOM

1190

OD2

ASP

A

155

−17.698

−47.398

10.585

1.00

113.72

A

O

ATOM

1191

C

ASP

A

155

−16.962

−48.780

6.781

1.00

113.43

A

C

ATOM

1192

O

ASP

A

155

−16.954

−47.730

6.126

1.00

113.49

A

O

ATOM

1193

N

ASP

A

156

−15.960

−49.654

6.760

1.00

113.13

A

N

ATOM

1194

CA

ASP

A

156

−14.741

−49.429

5.992

1.00

113.04

A

C

ATOM

1195

CB

ASP

A

156

−13.518

−49.876

6.799

1.00

113.50

A

C

ATOM

1196

CG

ASP

A

156

−13.350

−49.089

8.098

1.00

115.24

A

C

ATOM

1197

OD1

ASP

A

156

−12.995

−47.881

8.025

1.00

116.26

A

O

ATOM

1198

OD2

ASP

A

156

−13.564

−49.687

9.188

1.00

116.50

A

O

ATOM

1199

C

ASP

A

156

−14.761

−50.141

4.637

1.00

112.37

A

C

ATOM

1200

O

ASP

A

156

−14.457

−49.521

3.598

1.00

112.39

A

O

ATOM

1201

N

ASP

A

157

−15.138

−51.428

4.661

1.00

111.11

A

N

ATOM

1202

CA

ASP

A

157

−15.032

−52.352

3.511

1.00

109.57

A

C

ATOM

1203

CB

ASP

A

157

−15.718

−53.683

3.837

1.00

109.55

A

C

ATOM

1204

CG

ASP

A

157

−15.232

−54.287

5.131

1.00

109.55

A

C

ATOM

1205

OD1

ASP

A

157

−14.007

−54.299

5.353

1.00

110.05

A

O

ATOM

1206

OD2

ASP

A

157

−16.074

−54.755

5.926

1.00

109.20

A

O

ATOM

1207

C

ASP

A

157

−15.578

−51.824

2.177

1.00

108.49

A

C

ATOM

1208

O

ASP

A

157

−16.474

−50.965

2.153

1.00

108.32

A

O

ATOM

1209

N

LEU

A

158

−15.018

−52.346

1.080

1.00

106.93

A

N

ATOM

1210

CA

LEU

A

158

−15.535

−52.120

−0.278

1.00

105.21

A

C

ATOM

1211

CB

LEU

A

158

−14.510

−51.420

−1.162

1.00

105.22

A

C

ATOM

1212

CG

LEU

A

158

−14.669

−49.922

−1.397

1.00

104.64

A

C

ATOM

1213

CD1

LEU

A

158

−14.210

−49.144

−0.179

1.00

104.82

A

C

ATOM

1214

CD2

LEU

A

158

−13.855

−49.536

−2.611

1.00

104.32

A

C

ATOM

1215

C

LEU

A

158

−15.949

−53.425

−0.937

1.00

104.15

A

C

ATOM

1216

O

LEU

A

158

−15.259

−54.446

−0.800

1.00

103.80

A

O

ATOM

1217

N

PHE

A

159

−17.073

−53.369

−1.657

1.00

102.77

A

N

ATOM

1218

CA

PHE

A

159

−17.702

−54.549

−2.248

1.00

101.04

A

C

ATOM

1219

CB

PHE

A

159

−19.193

−54.553

−1.927

1.00

101.03

A

C

ATOM

1220

CG

PHE

A

159

−19.898

−55.809

−2.336

1.00

100.64

A

C

ATOM

1221

CD1

PHE

A

159

−20.085

−56.835

−1.429

1.00

100.74

A

C

ATOM

1222

CE1

PHE

A

159

−20.743

−58.009

−1.799

1.00

100.39

A

C

ATOM

1223

CZ

PHE

A

159

−21.213

−58.161

−3.089

1.00

100.62

A

C

ATOM

1224

CE2

PHE

A

159

−21.034

−57.137

−4.008

1.00

101.11

A

C

ATOM

1225

CD2

PHE

A

159

−20.384

−55.966

−3.625

1.00

101.01

A

C

ATOM

1226

C

PHE

A

159

−17.529

−54.554

−3.747

1.00

99.89

A

C

ATOM

1227

O

PHE

A

159

−17.535

−53.494

−4.372

1.00

99.93

A

O

ATOM

1228

N

VAL

A

160

−17.379

−55.752

−4.310

1.00

98.31

A

N

ATOM

1229

CA

VAL

A

160

−17.427

−55.959

−5.758

1.00

96.89

A

C

ATOM

1230

CB

VAL

A

160

−16.051

−55.744

−6.425

1.00

96.76

A

C

ATOM

1231

CG1

VAL

A

160

−15.769

−56.808

−7.421

1.00

97.04

A

C

ATOM

1232

CG2

VAL

A

160

−15.990

−54.408

−7.102

1.00

96.85

A

C

ATOM

1233

C

VAL

A

160

−18.004

−57.323

−6.133

1.00

96.03

A

C

ATOM

1234

O

VAL

A

160

−17.438

−58.373

−5.814

1.00

95.68

A

O

ATOM

1235

N

ASP

A

161

−19.154

−57.297

−6.796

1.00

95.18

A

N

ATOM

1236

CA

ASP

A

161

−19.655

−58.472

−7.489

1.00

94.25

A

C

ATOM

1237

CB

ASP

A

161

−21.134

−58.335

−7.789

1.00

93.70

A

C

ATOM

1238

CG

ASP

A

161

−21.758

−59.651

−8.166

1.00

93.95

A

C

ATOM

1239

OD1

ASP

A

161

−20.989

−60.600

−8.470

1.00

93.40

A

O

ATOM

1240

OD2

ASP

A

161

−23.013

−59.749

−8.143

1.00

93.73

A

O

ATOM

1241

C

ASP

A

161

−18.868

−58.710

−8.793

1.00

94.03

A

C

ATOM

1242

O

ASP

A

161

−18.755

−57.843

−9.662

1.00

94.26

A

O

ATOM

1243

N

LEU

A

162

−18.295

−59.892

−8.914

1.00

93.43

A

N

ATOM

1244

CA

LEU

A

162

−17.558

−60.233

−10.106

1.00

92.67

A

C

ATOM

1245

CB

LEU

A

162

−16.258

−60.959

−9.755

1.00

92.01

A

C

ATOM

1246

CG

LEU

A

162

−15.128

−60.147

−9.126

1.00

90.25

A

C

ATOM

1247

CD1

LEU

A

162

−13.916

−61.024

−8.999

1.00

89.47

A

C

ATOM

1248

CD2

LEU

A

162

−14.790

−58.927

−9.923

1.00

88.14

A

C

ATOM

1249

C

LEU

A

162

−18.465

−61.097

−10.986

1.00

92.95

A

C

ATOM

1250

O

LEU

A

162

−18.862

−62.215

−10.598

1.00

93.15

A

O

ATOM

1251

N

GLY

A

163

−18.798

−60.566

−12.164

1.00

92.36

A

N

ATOM

1252

CA

GLY

A

163

−19.824

−61.172

−12.992

1.00

91.64

A

C

ATOM

1253

C

GLY

A

163

−21.166

−60.668

−12.512

1.00

90.99

A

C

ATOM

1254

O

GLY

A

163

−22.100

−61.451

−12.250

1.00

90.87

A

O

ATOM

1255

N

SER

A

164

−21.242

−59.345

−12.410

1.00

90.03

A

N

ATOM

1256

CA

SER

A

164

−22.336

−58.651

−11.755

1.00

89.75

A

C

ATOM

1257

CB

SER

A

164

−22.037

−57.149

−11.728

1.00

89.72

A

C

ATOM

1258

OG

SER

A

164

−23.203

−56.352

−11.702

1.00

89.77

A

O

ATOM

1259

C

SER

A

164

−23.744

−58.925

−12.291

1.00

89.68

A

C

ATOM

1260

O

SER

A

164

−24.703

−58.886

−11.519

1.00

89.75

A

O

ATOM

1261

N

GLY

A

165

−23.865

−59.195

−13.594

1.00

89.66

A

N

ATOM

1262

CA

GLY

A

165

−25.167

−59.400

−14.251

1.00

89.34

A

C

ATOM

1263

C

GLY

A

165

−26.010

−58.137

−14.258

1.00

89.44

A

C

ATOM

1264

O

GLY

A

165

−25.505

−57.029

−14.458

1.00

89.26

A

O

ATOM

1265

N

VAL

A

166

−27.306

−58.301

−14.027

1.00

89.52

A

N

ATOM

1266

CA

VAL

A

166

−28.186

−57.155

−13.844

1.00

89.54

A

C

ATOM

1267

CB

VAL

A

166

−29.652

−57.540

−13.915

1.00

89.66

A

C

ATOM

1268

CG1

VAL

A

166

−30.143

−57.404

−15.347

1.00

90.17

A

C

ATOM

1269

CG2

VAL

A

166

−29.867

−58.961

−13.379

1.00

90.05

A

C

ATOM

1270

C

VAL

A

166

−27.903

−56.473

−12.524

1.00

89.50

A

C

ATOM

1271

O

VAL

A

166

−28.244

−55.297

−12.353

1.00

89.71

A

O

ATOM

1272

N

GLY

A

167

−27.293

−57.227

−11.602

1.00

89.39

A

N

ATOM

1273

CA

GLY

A

167

−26.671

−56.686

−10.387

1.00

88.93

A

C

ATOM

1274

C

GLY

A

167

−27.615

−56.436

−9.238

1.00

88.64

A

C

ATOM

1275

O

GLY

A

167

−27.595

−55.366

−8.638

1.00

88.15

A

O

ATOM

1276

N

GLN

A

168

−28.446

−57.435

−8.947

1.00

88.78

A

N

ATOM

1277

CA

GLN

A

168

−29.392

−57.384

−7.829

1.00

88.88

A

C

ATOM

1278

CB

GLN

A

168

−30.480

−58.460

−7.959

1.00

88.65

A

C

ATOM

1279

CG

GLN

A

168

−30.000

−59.896

−8.038

1.00

88.34

A

C

ATOM

1280

CD

GLN

A

168

−29.562

−60.314

−9.432

1.00

89.15

A

C

ATOM

1281

OE1

GLN

A

168

−28.919

−59.551

−10.155

1.00

89.95

A

O

ATOM

1282

NE2

GLN

A

168

−29.886

−61.544

−9.806

1.00

89.52

A

N

ATOM

1283

C

GLN

A

168

−28.687

−57.467

−6.477

1.00

88.97

A

C

ATOM

1284

O

GLN

A

168

−29.134

−56.870

−5.499

1.00

89.12

A

O

ATOM

1285

N

VAL

A

169

−27.570

−58.181

−6.439

1.00

89.02

A

N

ATOM

1286

CA

VAL

A

169

−26.742

−58.216

−5.247

1.00

89.32

A

C

ATOM

1287

CB

VAL

A

169

−25.693

−59.314

−5.329

1.00

89.26

A

C

ATOM

1288

CG1

VAL

A

169

−24.692

−59.173

−4.199

1.00

88.94

A

C

ATOM

1289

CG2

VAL

A

169

−26.376

−60.676

−5.277

1.00

89.18

A

C

ATOM

1290

C

VAL

A

169

−26.111

−56.862

−4.928

1.00

89.64

A

C

ATOM

1291

O

VAL

A

169

−26.336

−56.319

−3.857

1.00

89.90

A

O

ATOM

1292

N

VAL

A

170

−25.350

−56.301

−5.859

1.00

90.19

A

N

ATOM

1293

CA

VAL

A

170

−24.801

−54.947

−5.696

1.00

90.63

A

C

ATOM

1294

CB

VAL

A

170

−24.475

−54.295

−7.047

1.00

90.31

A

C

ATOM

1295

CG1

VAL

A

170

−23.230

−53.452

−6.927

1.00

90.60

A

C

ATOM

1296

CG2

VAL

A

170

−24.298

−55.333

−8.107

1.00

90.38

A

C

ATOM

1297

C

VAL

A

170

−25.829

−54.047

−5.031

1.00

91.10

A

C

ATOM

1298

O

VAL

A

170

−25.522

−53.219

−4.177

1.00

90.88

A

O

ATOM

1299

N

LEU

A

171

−27.067

−54.218

−5.442

1.00

92.06

A

N

ATOM

1300

CA

LEU

A

171

−28.100

−53.381

−4.939

1.00

93.36

A

C

ATOM

1301

CB

LEU

A

171

−29.353

−53.516

−5.804

1.00

93.25

A

C

ATOM

1302

CG

LEU

A

171

−29.367

−52.773

−7.138

1.00

92.41

A

C

ATOM

1303

CD1

LEU

A

171

−30.755

−52.865

−7.705

1.00

92.69

A

C

ATOM

1304

CD2

LEU

A

171

−28.956

−51.318

−6.992

1.00

90.99

A

C

ATOM

1305

C

LEU

A

171

−28.363

−53.764

−3.494

1.00

94.42

A

C

ATOM

1306

O

LEU

A

171

−28.341

−52.909

−2.598

1.00

94.55

A

O

ATOM

1307

N

GLN

A

172

−28.590

−55.055

−3.277

1.00

95.39

A

N

ATOM

1308

CA

GLN

A

172

−28.908

−55.561

−1.960

1.00

96.41

A

C

ATOM

1309

CB

GLN

A

172

−29.049

−57.067

−2.007

1.00

95.92

A

C

ATOM

1310

CG

GLN

A

172

−29.323

−57.649

−0.662

1.00

96.66

A

C

ATOM

1311

CD

GLN

A

172

−29.583

−59.119

−0.713

1.00

97.85

A

C

ATOM

1312

OE1

GLN

A

172

−29.656

−59.707

−1.797

1.00

99.40

A

O

ATOM

1313

NE2

GLN

A

172

−29.737

−59.736

0.460

1.00

97.11

A

N

ATOM

1314

C

GLN

A

172

−27.839

−55.155

−0.945

1.00

97.40

A

C

ATOM

1315

O

GLN

A

172

−28.157

−54.701

0.157

1.00

98.00

A

O

ATOM

1316

N

VAL

A

173

−26.578

−55.295

−1.336

1.00

98.25

A

N

ATOM

1317

CA

VAL

A

173

−25.457

−54.975

−0.475

1.00

99.24

A

C

ATOM

1318

CB

VAL

A

173

−24.141

−55.445

−1.105

1.00

99.10

A

C

ATOM

1319

CG1

VAL

A

173

−22.951

−55.016

−0.281

1.00

99.19

A

C

ATOM

1320

CG2

VAL

A

173

−24.158

−56.945

−1.236

1.00

98.87

A

C

ATOM

1321

C

VAL

A

173

−25.419

−53.491

−0.130

1.00

100.37

A

C

ATOM

1322

O

VAL

A

173

−25.061

−53.119

0.984

1.00

100.55

A

O

ATOM

1323

N

ALA

A

174

−25.811

−52.639

−1.071

1.00

101.89

A

N

ATOM

1324

CA

ALA

A

174

−25.938

−51.208

−0.775

1.00

103.35

A

C

ATOM

1325

CB

ALA

A

174

−26.325

−50.428

−2.032

1.00

103.04

A

C

ATOM

1326

C

ALA

A

174

−26.957

−50.974

0.348

1.00

104.32

A

C

ATOM

1327

O

ALA

A

174

−26.767

−50.134

1.225

1.00

104.29

A

O

ATOM

1328

N

ALA

A

175

−28.021

−51.759

0.326

1.00

105.84

A

N

ATOM

1329

CA

ALA

A

175

−29.140

−51.555

1.215

1.00

107.44

A

C

ATOM

1330

CB

ALA

A

175

−30.410

−52.069

0.561

1.00

107.37

A

C

ATOM

1331

C

ALA

A

175

−28.944

−52.209

2.576

1.00

108.63

A

C

ATOM

1332

O

ALA

A

175

−29.691

−51.925

3.521

1.00

109.14

A

O

ATOM

1333

N

ALA

A

176

−27.958

−53.092

2.683

1.00

109.75

A

N

ATOM

1334

CA

ALA

A

176

−27.764

−53.832

3.925

1.00

110.82

A

C

ATOM

1335

CB

ALA

A

176

−27.731

−55.320

3.646

1.00

110.63

A

C

ATOM

1336

C

ALA

A

176

−26.513

−53.385

4.681

1.00

111.70

A

C

ATOM

1337

O

ALA

A

176

−26.455

−53.462

5.908

1.00

111.87

A

O

ATOM

1338

N

THR

A

177

−25.533

−52.893

3.935

1.00

112.83

A

N

ATOM

1339

CA

THR

A

177

−24.221

−52.581

4.466

1.00

114.01

A

C

ATOM

1340

CB

THR

A

177

−23.171

−53.374

3.725

1.00

113.89

A

C

ATOM

1341

OG1

THR

A

177

−23.074

−52.872

2.383

1.00

113.58

A

O

ATOM

1342

CG2

THR

A

177

−23.537

−54.861

3.702

1.00

113.55

A

C

ATOM

1343

C

THR

A

177

−23.904

−51.115

4.235

1.00

115.31

A

C

ATOM

1344

O

THR

A

177

−24.268

−50.550

3.201

1.00

115.83

A

O

ATOM

1345

N

ASN

A

178

−23.200

−50.497

5.173

1.00

116.62

A

N

ATOM

1346

CA

ASN

A

178

−22.938

−49.065

5.065

1.00

117.94

A

C

ATOM

1347

CB

ASN

A

178

−23.345

−48.314

6.354

1.00

118.42

A

C

ATOM

1348

CG

ASN

A

178

−22.546

−48.749

7.586

1.00

119.90

A

C

ATOM

1349

OD1

ASN

A

178

−21.735

−47.973

8.109

1.00

121.25

A

O

ATOM

1350

ND2

ASN

A

178

−22.776

−49.984

8.057

1.00

120.57

A

N

ATOM

1351

C

ASN

A

178

−21.516

−48.727

4.637

1.00

118.23

A

C

ATOM

1352

O

ASN

A

178

−20.571

−48.853

5.422

1.00

118.38

A

O

ATOM

1353

N

CYS

A

179

−21.367

−48.307

3.382

1.00

118.67

A

N

ATOM

1354

CA

CYS

A

179

−20.056

−47.893

2.871

1.00

119.18

A

C

ATOM

1355

CB

CYS

A

179

−19.221

−49.113

2.484

1.00

119.20

A

C

ATOM

1356

SG

CYS

A

179

−19.810

−50.646

3.221

1.00

120.25

A

S

ATOM

1357

C

CYS

A

179

−20.145

−46.935

1.688

1.00

119.12

A

C

ATOM

1358

O

CYS

A

179

−21.235

−46.548

1.260

1.00

118.98

A

O

ATOM

1359

N

LYS

A

180

−18.981

−46.548

1.176

1.00

119.12

A

N

ATOM

1360

CA

LYS

A

180

−18.923

−45.749

−0.034

1.00

119.11

A

C

ATOM

1361

CB

LYS

A

180

−17.622

−44.932

−0.121

1.00

119.54

A

C

ATOM

1362

CG

LYS

A

180

−17.378

−43.953

1.035

1.00

120.14

A

C

ATOM

1363

CD

LYS

A

180

−16.267

−44.463

1.977

1.00

120.95

A

C

ATOM

1364

CE

LYS

A

180

−16.407

−43.901

3.399

1.00

121.10

A

C

ATOM

1365

NZ

LYS

A

180

−16.393

−42.407

3.477

1.00

120.94

A

N

ATOM

1366

C

LYS

A

180

−19.052

−46.691

−1.220

1.00

118.65

A

C

ATOM

1367

O

LYS

A

180

−19.071

−47.906

−1.046

1.00

118.49

A

O

ATOM

1368

N

HIS

A

181

−19.144

−46.107

−2.411

1.00

118.21

A

N

ATOM

1369

CA

HIS

A

181

−19.338

−46.817

−3.676

1.00

118.03

A

C

ATOM

1370

CB

HIS

A

181

−18.523

−46.147

−4.784

1.00

118.24

A

C

ATOM

1371

CG

HIS

A

181

−19.316

−45.196

−5.615

1.00

118.88

A

C

ATOM

1372

ND1

HIS

A

181

−19.200

−43.828

−5.495

1.00

120.41

A

N

ATOM

1373

CE1

HIS

A

181

−20.029

−43.242

−6.340

1.00

120.88

A

C

ATOM

1374

NE2

HIS

A

181

−20.682

−44.183

−6.999

1.00

121.22

A

N

ATOM

1375

CD2

HIS

A

181

−20.255

−45.415

−6.564

1.00

119.69

A

C

ATOM

1376

C

HIS

A

181

−19.056

−48.314

−3.695

1.00

117.64

A

C

ATOM

1377

O

HIS

A

181

−17.902

−48.738

−3.552

1.00

117.82

A

O

ATOM

1378

N

HIS

A

182

−20.110

−49.103

−3.892

1.00

116.90

A

N

ATOM

1379

CA

HIS

A

182

−19.946

−50.516

−4.197

1.00

116.61

A

C

ATOM

1380

CB

HIS

A

182

−20.924

−51.381

−3.407

1.00

116.68

A

C

ATOM

1381

CG

HIS

A

182

−20.996

−51.045

−1.951

1.00

116.92

A

C

ATOM

1382

ND1

HIS

A

182

−22.141

−51.222

−1.205

1.00

116.98

A

N

ATOM

1383

CE1

HIS

A

182

−21.915

−50.843

0.039

1.00

117.13

A

C

ATOM

1384

NE2

HIS

A

182

−20.668

−50.417

0.124

1.00

117.31

A

N

ATOM

1385

CD2

HIS

A

182

−20.068

−50.542

−1.104

1.00

116.96

A

C

ATOM

1386

C

HIS

A

182

−20.172

−50.711

−5.683

1.00

116.30

A

C

ATOM

1387

O

HIS

A

182

−21.162

−50.229

−6.221

1.00

116.37

A

O

ATOM

1388

N

TYR

A

183

−19.257

−51.410

−6.345

1.00

115.91

A

N

ATOM

1389

CA

TYR

A

183

−19.351

−51.597

−7.783

1.00

115.59

A

C

ATOM

1390

CB

TYR

A

183

−18.004

−51.367

−8.452

1.00

115.48

A

C

ATOM

1391

CG

TYR

A

183

−17.325

−50.061

−8.116

1.00

115.78

A

C

ATOM

1392

CD1

TYR

A

183

−15.975

−50.038

−7.766

1.00

116.65

A

C

ATOM

1393

CE1

TYR

A

183

−15.326

−48.844

−7.469

1.00

116.84

A

C

ATOM

1394

CZ

TYR

A

183

−16.034

−47.653

−7.517

1.00

116.46

A

C

ATOM

1395

OH

TYR

A

183

−15.375

−46.484

−7.215

1.00

116.73

A

O

ATOM

1396

CE2

TYR

A

183

−17.380

−47.645

−7.870

1.00

115.67

A

C

ATOM

1397

CD2

TYR

A

183

−18.015

−48.848

−8.166

1.00

115.39

A

C

ATOM

1398

C

TYR

A

183

−19.846

−52.973

−8.171

1.00

115.62

A

C

ATOM

1399

O

TYR

A

183

−19.611

−53.950

−7.457

1.00

115.63

A

O

ATOM

1400

N

GLY

A

184

−20.542

−53.031

−9.304

1.00

115.57

A

N

ATOM

1401

CA

GLY

A

184

−20.787

−54.281

−10.026

1.00

115.67

A

C

ATOM

1402

C

GLY

A

184

−20.034

−54.184

−11.341

1.00

115.85

A

C

ATOM

1403

O

GLY

A

184

−19.654

−53.083

−11.748

1.00

116.15

A

O

ATOM

1404

N

VAL

A

185

−19.804

−55.313

−12.010

1.00

115.80

A

N

ATOM

1405

CA

VAL

A

185

−19.044

−55.317

−13.272

1.00

115.81

A

C

ATOM

1406

CB

VAL

A

185

−17.518

−55.359

−13.011

1.00

115.80

A

C

ATOM

1407

CG1

VAL

A

185

−17.076

−56.700

−12.417

1.00

116.35

A

C

ATOM

1408

CG2

VAL

A

185

−16.768

−55.075

−14.271

1.00

116.42

A

C

ATOM

1409

C

VAL

A

185

−19.466

−56.386

−14.297

1.00

115.87

A

C

ATOM

1410

O

VAL

A

185

−19.285

−57.598

−14.085

1.00

115.67

A

O

ATOM

1411

N

GLU

A

186

−20.015

−55.920

−15.417

1.00

116.18

A

N

ATOM

1412

CA

GLU

A

186

−20.541

−56.808

−16.466

1.00

116.46

A

C

ATOM

1413

CB

GLU

A

186

−22.044

−56.572

−16.635

1.00

116.05

A

C

ATOM

1414

CG

GLU

A

186

−22.712

−57.512

−17.616

1.00

115.22

A

C

ATOM

1415

CD

GLU

A

186

−22.916

−58.897

−17.045

1.00

114.43

A

C

ATOM

1416

OE1

GLU

A

186

−23.105

−59.863

−17.821

1.00

114.59

A

O

ATOM

1417

OE2

GLU

A

186

−22.880

−59.025

−15.809

1.00

113.03

A

O

ATOM

1418

C

GLU

A

186

−19.841

−56.633

−17.825

1.00

116.82

A

C

ATOM

1419

O

GLU

A

186

−19.753

−55.510

−18.335

1.00

117.07

A

O

ATOM

1420

N

LYS

A

187

−19.358

−57.734

−18.407

1.00

116.78

A

N

ATOM

1421

CA

LYS

A

187

−18.791

−57.708

−19.759

1.00

116.96

A

C

ATOM

1422

CB

LYS

A

187

−17.916

−58.943

−20.026

1.00

116.49

A

C

ATOM

1423

CG

LYS

A

187

−18.690

−60.273

−20.173

1.00

115.13

A

C

ATOM

1424

CD

LYS

A

187

−17.835

−61.509

−19.961

1.00

111.66

A

C

ATOM

1425

CE

LYS

A

187

−16.452

−61.341

−20.558

1.00

110.54

A

C

ATOM

1426

NZ

LYS

A

187

−15.650

−62.590

−20.439

1.00

110.61

A

N

ATOM

1427

C

LYS

A

187

−19.890

−57.570

−20.829

1.00

117.82

A

C

ATOM

1428

O

LYS

A

187

−19.894

−56.609

−21.604

1.00

118.10

A

O

ATOM

1429

N

ALA

A

188

−20.835

−58.512

−20.835

1.00

118.56

A

N

ATOM

1430

CA

ALA

A

188

−21.835

−58.645

−21.900

1.00

119.22

A

C

ATOM

1431

CB

ALA

A

188

−22.487

−60.029

−21.831

1.00

119.05

A

C

ATOM

1432

C

ALA

A

188

−22.911

−57.560

−21.888

1.00

119.73

A

C

ATOM

1433

O

ALA

A

188

−23.427

−57.211

−20.830

1.00

120.05

A

O

ATOM

1434

N

ASP

A

189

−23.248

−57.037

−23.070

1.00

120.41

A

N

ATOM

1435

CA

ASP

A

189

−24.433

−56.182

−23.245

1.00

120.80

A

C

ATOM

1436

CB

ASP

A

189

−24.507

−55.635

−24.674

1.00

120.73

A

C

ATOM

1437

CG

ASP

A

189

−23.508

−54.521

−24.931

0.50

121.31

A

C

ATOM

1438

OD1

ASP

A

189

−23.930

−53.471

−25.465

0.50

121.74

A

O

ATOM

1439

OD2

ASP

A

189

−22.308

−54.686

−24.608

0.50

121.55

A

O

ATOM

1440

C

ASP

A

189

−25.704

−56.973

−22.934

1.00

121.02

A

C

ATOM

1441

O

ASP

A

189

−25.752

−58.198

−23.123

1.00

121.02

A

O

ATOM

1442

N

ILE

A

190

−26.725

−56.269

−22.457

1.00

121.16

A

N

ATOM

1443

CA

ILE

A

190

−28.016

−56.879

−22.104

1.00

121.57

A

C

ATOM

1444

CB

ILE

A

190

−28.417

−58.094

−23.040

1.00

121.61

A

C

ATOM

1445

CG1

ILE

A

190

−28.973

−57.569

−24.370

1.00

122.31

A

C

ATOM

1446

CD1

ILE

A

190

−30.163

−56.566

−24.238

1.00

122.33

A

C

ATOM

1447

CG2

ILE

A

190

−29.430

−59.044

−22.383

1.00

121.88

A

C

ATOM

1448

C

ILE

A

190

−28.165

−57.117

−20.586

1.00

121.52

A

C

ATOM

1449

O

ILE

A

190

−28.927

−56.379

−19.947

1.00

121.71

A

O

ATOM

1450

N

PRO

A

191

−27.433

−58.100

−19.992

1.00

121.32

A

N

ATOM

1451

CA

PRO

A

191

−27.423

−58.050

−18.536

1.00

121.10

A

C

ATOM

1452

CB

PRO

A

191

−26.406

−59.125

−18.165

1.00

120.97

A

C

ATOM

1453

CG

PRO

A

191

−26.504

−60.095

−19.260

1.00

121.02

A

C

ATOM

1454

CD

PRO

A

191

−26.649

−59.249

−20.483

1.00

121.26

A

C

ATOM

1455

C

PRO

A

191

−26.933

−56.669

−18.116

1.00

121.02

A

C

ATOM

1456

O

PRO

A

191

−27.480

−56.060

−17.187

1.00

120.91

A

O

ATOM

1457

N

ALA

A

192

−25.937

−56.178

−18.849

1.00

120.88

A

N

ATOM

1458

CA

ALA

A

192

−25.456

−54.816

−18.717

1.00

120.90

A

C

ATOM

1459

CB

ALA

A

192

−24.295

−54.581

−19.653

1.00

120.94

A

C

ATOM

1460

C

ALA

A

192

−26.542

−53.781

−18.973

1.00

120.92

A

C

ATOM

1461

O

ALA

A

192

−26.573

−52.750

−18.296

1.00

120.99

A

O

ATOM

1462

N

LYS

A

193

−27.416

−54.037

−19.949

1.00

120.89

A

N

ATOM

1463

CA

LYS

A

193

−28.392

−53.020

−20.337

1.00

120.94

A

C

ATOM

1464

CB

LYS

A

193

−28.899

−53.189

−21.769

1.00

121.13

A

C

ATOM

1465

CG

LYS

A

193

−29.418

−51.862

−22.363

1.00

121.57

A

C

ATOM

1466

CD

LYS

A

193

−30.216

−52.038

−23.665

1.00

122.00

A

C

ATOM

1467

CE

LYS

A

193

−31.673

−52.438

−23.423

1.00

121.21

A

C

ATOM

1468

NZ

LYS

A

193

−31.810

−53.872

−23.054

1.00

120.87

A

N

ATOM

1469

C

LYS

A

193

−29.544

−52.964

−19.365

1.00

120.80

A

C

ATOM

1470

O

LYS

A

193

−29.986

−51.876

−18.988

1.00

120.78

A

O

ATOM

1471

N

TYR

A

194

−30.020

−54.137

−18.954

1.00

120.62

A

N

ATOM

1472

CA

TYR

A

194

−31.013

−54.215

−17.890

1.00

120.56

A

C

ATOM

1473

CB

TYR

A

194

−31.475

−55.655

−17.655

1.00

120.57

A

C

ATOM

1474

CG

TYR

A

194

−32.246

−56.279

−18.810

1.00

121.31

A

C

ATOM

1475

CD1

TYR

A

194

−33.095

−55.511

−19.623

1.00

122.05

A

C

ATOM

1476

CE1

TYR

A

194

−33.809

−56.089

−20.676

1.00

122.46

A

C

ATOM

1477

CZ

TYR

A

194

−33.682

−57.451

−20.916

1.00

123.31

A

C

ATOM

1478

OH

TYR

A

194

−34.377

−58.046

−21.950

1.00

124.42

A

O

ATOM

1479

CE2

TYR

A

194

−32.856

−58.232

−20.117

1.00

122.66

A

C

ATOM

1480

CD2

TYR

A

194

−32.149

−57.645

−19.072

1.00

121.80

A

C

ATOM

1481

C

TYR

A

194

−30.457

−53.590

−16.611

1.00

120.30

A

C

ATOM

1482

O

TYR

A

194

−31.135

−52.796

−15.958

1.00

120.27

A

O

ATOM

1483

N

ALA

A

195

−29.207

−53.910

−16.287

1.00

119.98

A

N

ATOM

1484

CA

ALA

A

195

−28.512

−53.254

−15.183

1.00

119.75

A

C

ATOM

1485

CB

ALA

A

195

−27.052

−53.581

−15.221

1.00

119.76

A

C

ATOM

1486

C

ALA

A

195

−28.702

−51.739

−15.168

1.00

119.74

A

C

ATOM

1487

O

ALA

A

195

−28.616

−51.118

−14.110

1.00

119.86

A

O

ATOM

1488

N

GLU

A

196

−28.961

−51.145

−16.333

1.00

119.62

A

N

ATOM

1489

CA

GLU

A

196

−29.099

−49.689

−16.430

1.00

119.52

A

C

ATOM

1490

CB

GLU

A

196

−28.820

−49.204

−17.850

1.00

119.63

A

C

ATOM

1491

CG

GLU

A

196

−27.351

−49.006

−18.150

1.00

121.03

A

C

ATOM

1492

CD

GLU

A

196

−27.057

−48.974

−19.639

1.00

122.77

A

C

ATOM

1493

OE1

GLU

A

196

−27.477

−49.926

−20.346

1.00

123.35

A

O

ATOM

1494

OE2

GLU

A

196

−26.400

−48.002

−20.094

1.00

122.42

A

O

ATOM

1495

C

GLU

A

196

−30.462

−49.206

−15.967

1.00

119.08

A

C

ATOM

1496

O

GLU

A

196

−30.581

−48.136

−15.357

1.00

118.95

A

O

ATOM

1497

N

THR

A

197

−31.491

−49.990

−16.277

1.00

118.57

A

N

ATOM

1498

CA

THR

A

197

−32.840

−49.682

−15.821

1.00

118.04

A

C

ATOM

1499

CB

THR

A

197

−33.911

−50.366

−16.673

1.00

117.83

A

C

ATOM

1500

OG1

THR

A

197

−33.365

−51.545

−17.267

1.00

117.85

A

O

ATOM

1501

CG2

THR

A

197

−34.338

−49.449

−17.776

1.00

118.30

A

C

ATOM

1502

C

THR

A

197

−32.997

−50.061

−14.354

1.00

117.68

A

C

ATOM

1503

O

THR

A

197

−33.696

−49.363

−13.603

1.00

117.87

A

O

ATOM

1504

N

MET

A

198

−32.326

−51.150

−13.954

1.00

116.83

A

N

ATOM

1505

CA

MET

A

198

−32.321

−51.617

−12.565

1.00

115.79

A

C

ATOM

1506

CB

MET

A

198

−31.492

−52.891

−12.417

1.00

115.62

A

C

ATOM

1507

CG

MET

A

198

−32.140

−54.125

−12.999

1.00

115.16

A

C

ATOM

1508

SD

MET

A

198

−33.212

−54.988

−11.832

1.00

115.70

A

S

ATOM

1509

CE

MET

A

198

−32.296

−56.491

−11.518

1.00

114.02

A

C

ATOM

1510

C

MET

A

198

−31.787

−50.513

−11.662

1.00

115.30

A

C

ATOM

1511

O

MET

A

198

−32.407

−50.164

−10.663

1.00

115.13

A

O

ATOM

1512

N

ASP

A

199

−30.649

−49.945

−12.042

1.00

114.78

A

N

ATOM

1513

CA

ASP

A

199

−30.106

−48.795

−11.352

1.00

114.49

A

C

ATOM

1514

CB

ASP

A

199

−28.990

−48.168

−12.199

1.00

114.49

A

C

ATOM

1515

CG

ASP

A

199

−28.398

−46.899

−11.580

1.00

114.62

A

C

ATOM

1516

OD1

ASP

A

199

−29.155

−46.019

−11.106

1.00

114.42

A

O

ATOM

1517

OD2

ASP

A

199

−27.154

−46.769

−11.600

1.00

115.05

A

O

ATOM

1518

C

ASP

A

199

−31.240

−47.804

−11.092

1.00

114.33

A

C

ATOM

1519

O

ASP

A

199

−31.494

−47.428

−9.947

1.00

114.33

A

O

ATOM

1520

N

ARG

A

200

−31.940

−47.414

−12.153

1.00

114.07

A

N

ATOM

1521

CA

ARG

A

200

−32.932

−46.355

−12.057

1.00

113.96

A

C

ATOM

1522

CB

ARG

A

200

−33.461

−45.973

−13.440

1.00

114.31

A

C

ATOM

1523

CG

ARG

A

200

−32.411

−45.390

−14.368

1.00

116.73

A

C

ATOM

1524

CD

ARG

A

200

−33.044

−44.603

−15.534

1.00

120.46

A

C

ATOM

1525

NE

ARG

A

200

−32.155

−44.582

−16.701

1.00

122.27

A

N

ATOM

1526

CZ

ARG

A

200

−32.205

−45.459

−17.706

1.00

123.10

A

C

ATOM

1527

NH1

ARG

A

200

−33.113

−46.430

−17.720

1.00

123.10

A

N

ATOM

1528

NH2

ARG

A

200

−31.345

−45.360

−18.711

1.00

123.39

A

N

ATOM

1529

C

ARG

A

200

−34.083

−46.728

−11.130

1.00

113.15

A

C

ATOM

1530

O

ARG

A

200

−34.381

−46.005

−10.172

1.00

113.00

A

O

ATOM

1531

N

GLU

A

201

−34.714

−47.864

−11.412

1.00

112.21

A

N

ATOM

1532

CA

GLU

A

201

−35.940

−48.246

−10.720

1.00

111.28

A

C

ATOM

1533

CB

GLU

A

201

−36.543

−49.505

−11.338

1.00

111.13

A

C

ATOM

1534

CG

GLU

A

201

−37.504

−49.196

−12.471

1.00

111.12

A

C

ATOM

1535

CD

GLU

A

201

−38.923

−48.924

−11.990

1.00

111.43

A

C

ATOM

1536

OE1

GLU

A

201

−39.552

−49.865

−11.455

1.00

111.69

A

O

ATOM

1537

OE2

GLU

A

201

−39.418

−47.781

−12.159

1.00

111.10

A

O

ATOM

1538

C

GLU

A

201

−35.726

−48.396

−9.222

1.00

110.69

A

C

ATOM

1539

O

GLU

A

201

−36.505

−47.869

−8.425

1.00

110.74

A

O

ATOM

1540

N

PHE

A

202

−34.654

−49.091

−8.854

1.00

109.73

A

N

ATOM

1541

CA

PHE

A

202

−34.216

−49.188

−7.470

1.00

108.66

A

C

ATOM

1542

CB

PHE

A

202

−32.872

−49.901

−7.412

1.00

108.66

A

C

ATOM

1543

CG

PHE

A

202

−32.245

−49.910

−6.058

1.00

108.42

A

C

ATOM

1544

CD1

PHE

A

202

−32.506

−50.943

−5.170

1.00

108.11

A

C

ATOM

1545

CE1

PHE

A

202

−31.924

−50.964

−3.916

1.00

108.00

A

C

ATOM

1546

CZ

PHE

A

202

−31.063

−49.945

−3.542

1.00

108.70

A

C

ATOM

1547

CE2

PHE

A

202

−30.783

−48.903

−4.430

1.00

108.52

A

C

ATOM

1548

CD2

PHE

A

202

−31.371

−48.895

−5.678

1.00

108.42

A

C

ATOM

1549

C

PHE

A

202

−34.118

−47.810

−6.826

1.00

107.99

A

C

ATOM

1550

O

PHE

A

202

−34.761

−47.546

−5.813

1.00

107.92

A

O

ATOM

1551

N

ARG

A

203

−33.329

−46.927

−7.424

1.00

107.24

A

N

ATOM

1552

CA

ARG

A

203

−33.203

−45.569

−6.897

1.00

106.81

A

C

ATOM

1553

CB

ARG

A

203

−32.216

−44.736

−7.730

1.00

107.08

A

C

ATOM

1554

CG

ARG

A

203

−30.871

−44.517

−7.054

1.00

107.58

A

C

ATOM

1555

CD

ARG

A

203

−29.999

−43.561

−7.842

1.00

109.67

A

C

ATOM

1556

NE

ARG

A

203

−29.332

−42.582

−6.974

1.00

111.39

A

N

ATOM

1557

CZ

ARG

A

203

−29.803

−41.364

−6.681

1.00

112.22

A

C

ATOM

1558

NH1

ARG

A

203

−30.964

−40.932

−7.178

1.00

112.19

A

N

ATOM

1559

NH2

ARG

A

203

−29.106

−40.564

−5.881

1.00

112.60

A

N

ATOM

1560

C

ARG

A

203

−34.562

−44.866

−6.753

1.00

106.05

A

C

ATOM

1561

O

ARG

A

203

−34.808

−44.201

−5.744

1.00

106.01

A

O

ATOM

1562

N

LYS

A

204

−35.429

−45.038

−7.755

1.00

105.03

A

N

ATOM

1563

CA

LYS

A

204

−36.780

−44.481

−7.755

1.00

103.96

A

C

ATOM

1564

CB

LYS

A

204

−37.513

−44.881

−9.043

1.00

103.96

A

C

ATOM

1565

CG

LYS

A

204

−38.958

−44.366

−9.161

1.00

103.08

A

C

ATOM

1566

CD

LYS

A

204

−39.861

−45.332

−9.934

1.00

101.05

A

C

ATOM

1567

CE

LYS

A

204

−41.336

−45.048

−9.634

1.00

100.77

A

C

ATOM

1568

NZ

LYS

A

204

−42.221

−46.250

−9.779

1.00

99.07

A

N

ATOM

1569

C

LYS

A

204

−37.566

−44.978

−6.550

1.00

103.53

A

C

ATOM

1570

O

LYS

A

204

−38.099

−44.183

−5.772

1.00

103.25

A

O

ATOM

1571

N

TRP

A

205

−37.624

−46.302

−6.410

1.00

103.06

A

N

ATOM

1572

CA

TRP

A

205

−38.439

−46.960

−5.387

1.00

102.47

A

C

ATOM

1573

CB

TRP

A

205

−38.578

−48.448

−5.675

1.00

102.29

A

C

ATOM

1574

CG

TRP

A

205

−39.519

−48.757

−6.797

1.00

102.22

A

C

ATOM

1575

CD1

TRP

A

205

−39.190

−49.037

−8.089

1.00

102.24

A

C

ATOM

1576

NE1

TRP

A

205

−40.322

−49.286

−8.829

1.00

101.90

A

N

ATOM

1577

CE2

TRP

A

205

−41.412

−49.165

−8.014

1.00

102.02

A

C

ATOM

1578

CD2

TRP

A

205

−40.944

−48.834

−6.723

1.00

101.92

A

C

ATOM

1579

CE3

TRP

A

205

−41.872

−48.651

−5.694

1.00

101.93

A

C

ATOM

1580

CZ3

TRP

A

205

−43.219

−48.805

−5.978

1.00

102.20

A

C

ATOM

1581

CH2

TRP

A

205

−43.653

−49.133

−7.268

1.00

103.28

A

C

ATOM

1582

CZ2

TRP

A

205

−42.764

−49.316

−8.302

1.00

102.98

A

C

ATOM

1583

C

TRP

A

205

−37.923

−46.761

−3.972

1.00

102.18

A

C

ATOM

1584

O

TRP

A

205

−38.716

−46.686

−3.034

1.00

102.48

A

O

ATOM

1585

N

MET

A

206

−36.608

−46.669

−3.804

1.00

101.40

A

N

ATOM

1586

CA

MET

A

206

−36.079

−46.321

−2.497

1.00

100.76

A

C

ATOM

1587

CB

MET

A

206

−34.560

−46.268

−2.518

1.00

100.73

A

C

ATOM

1588

CG

MET

A

206

−33.930

−47.630

−2.740

1.00

101.36

A

C

ATOM

1589

SD

MET

A

206

−34.050

−48.770

−1.347

1.00

101.98

A

S

ATOM

1590

CE

MET

A

206

−32.528

−48.338

−0.501

1.00

101.91

A

C

ATOM

1591

C

MET

A

206

−36.688

−44.991

−2.084

1.00

100.35

A

C

ATOM

1592

O

MET

A

206

−37.366

−44.906

−1.064

1.00

100.12

A

O

ATOM

1593

N

LYS

A

207

−36.474

−43.975

−2.916

1.00

100.08

A

N

ATOM

1594

CA

LYS

A

207

−37.096

−42.667

−2.761

1.00

99.70

A

C

ATOM

1595

CB

LYS

A

207

−36.873

−41.821

−4.019

1.00

99.90

A

C

ATOM

1596

CG

LYS

A

207

−35.529

−41.111

−4.139

1.00

100.14

A

C

ATOM

1597

CD

LYS

A

207

−35.576

−40.137

−5.317

1.00

101.25

A

C

ATOM

1598

CE

LYS

A

207

−34.824

−38.834

−5.043

1.00

102.53

A

C

ATOM

1599

NZ

LYS

A

207

−35.447

−37.652

−5.745

1.00

101.98

A

N

ATOM

1600

C

LYS

A

207

−38.595

−42.804

−2.512

1.00

99.28

A

C

ATOM

1601

O

LYS

A

207

−39.138

−42.173

−1.603

1.00

99.44

A

O

ATOM

1602

N

TRP

A

208

−39.257

−43.634

−3.315

1.00

98.59

A

N

ATOM

1603

CA

TRP

A

208

−40.698

−43.836

−3.185

1.00

98.15

A

C

ATOM

1604

CB

TRP

A

208

−41.233

−44.757

−4.295

1.00

98.20

A

C

ATOM

1605

CG

TRP

A

208

−42.732

−44.649

−4.492

1.00

97.16

A

C

ATOM

1606

CD1

TRP

A

208

−43.397

−43.751

−5.292

1.00

97.28

A

C

ATOM

1607

NE1

TRP

A

208

−44.756

−43.944

−5.197

1.00

96.30

A

N

ATOM

1608

CE2

TRP

A

208

−44.992

−44.981

−4.333

1.00

95.28

A

C

ATOM

1609

CD2

TRP

A

208

−43.739

−45.449

−3.871

1.00

94.80

A

C

ATOM

1610

CE3

TRP

A

208

−43.708

−46.511

−2.971

1.00

93.47

A

C

ATOM

1611

CZ3

TRP

A

208

−44.906

−47.071

−2.563

1.00

93.20

A

C

ATOM

1612

CH2

TRP

A

208

−46.132

−46.592

−3.041

1.00

93.91

A

C

ATOM

1613

CZ2

TRP

A

208

−46.196

−45.549

−3.927

1.00

94.41

A

C

ATOM

1614

C

TRP

A

208

−41.086

−44.384

−1.813

1.00

97.98

A

C

ATOM

1615

O

TRP

A

208

−42.187

−44.127

−1.334

1.00

97.67

A

O

ATOM

1616

N

TYR

A

209

−40.167

−45.127

−1.191

1.00

97.95

A

N

ATOM

1617

CA

TYR

A

209

−40.391

−45.745

0.124

1.00

97.63

A

C

ATOM

1618

CB

TYR

A

209

−39.798

−47.139

0.146

1.00

96.50

A

C

ATOM

1619

CG

TYR

A

209

−40.619

−48.193

−0.539

1.00

93.33

A

C

ATOM

1620

CD1

TYR

A

209

−41.826

−48.637

0.000

1.00

89.99

A

C

ATOM

1621

CE1

TYR

A

209

−42.564

−49.631

−0.622

1.00

86.87

A

C

ATOM

1622

CZ

TYR

A

209

−42.087

−50.196

−1.790

1.00

85.75

A

C

ATOM

1623

OH

TYR

A

209

−42.774

−51.190

−2.427

1.00

83.47

A

O

ATOM

1624

CE2

TYR

A

209

−40.898

−49.783

−2.331

1.00

87.79

A

C

ATOM

1625

CD2

TYR

A

209

−40.166

−48.791

−1.703

1.00

90.72

A

C

ATOM

1626

C

TYR

A

209

−39.815

−44.968

1.311

1.00

98.60

A

C

ATOM

1627

O

TYR

A

209

−40.065

−45.322

2.460

1.00

98.54

A

O

ATOM

1628

N

GLY

A

210

−39.044

−43.923

1.027

1.00

99.66

A

N

ATOM

1629

CA

GLY

A

210

−38.359

−43.150

2.059

1.00

101.20

A

C

ATOM

1630

C

GLY

A

210

−37.095

−43.807

2.598

1.00

102.39

A

C

ATOM

1631

O

GLY

A

210

−36.742

−43.616

3.763

1.00

102.56

A

O

ATOM

1632

N

LYS

A

211

−36.404

−44.580

1.763

1.00

103.35

A

N

ATOM

1633

CA

LYS

A

211

−35.270

−45.363

2.247

1.00

104.29

A

C

ATOM

1634

CB

LYS

A

211

−35.512

−46.863

2.094

1.00

104.23

A

C

ATOM

1635

CG

LYS

A

211

−36.657

−47.423

2.940

1.00

104.42

A

C

ATOM

1636

CD

LYS

A

211

−36.666

−46.934

4.389

1.00

104.29

A

C

ATOM

1637

CE

LYS

A

211

−37.691

−47.730

5.190

1.00

105.06

A

C

ATOM

1638

NZ

LYS

A

211

−38.350

−46.951

6.276

1.00

105.66

A

N

ATOM

1639

C

LYS

A

211

−33.961

−44.985

1.604

1.00

105.08

A

C

ATOM

1640

O

LYS

A

211

−33.927

−44.478

0.481

1.00

105.23

A

O

ATOM

1641

N

LYS

A

212

−32.883

−45.246

2.338

1.00

106.18

A

N

ATOM

1642

CA

LYS

A

212

−31.553

−44.795

1.953

1.00

107.24

A

C

ATOM

1643

CB

LYS

A

212

−30.941

−43.922

3.055

1.00

107.38

A

C

ATOM

1644

CG

LYS

A

212

−30.584

−44.656

4.344

1.00

108.37

A

C

ATOM

1645

CD

LYS

A

212

−29.317

−44.061

4.932

1.00

110.33

A

C

ATOM

1646

CE

LYS

A

212

−29.045

−44.555

6.335

1.00

111.08

A

C

ATOM

1647

NZ

LYS

A

212

−28.434

−43.443

7.125

1.00

111.60

A

N

ATOM

1648

C

LYS

A

212

−30.623

−45.952

1.588

1.00

107.59

A

C

ATOM

1649

O

LYS

A

212

−30.681

−47.029

2.184

1.00

107.48

A

O

ATOM

1650

N

HIS

A

213

−29.773

−45.710

0.598

1.00

108.09

A

N

ATOM

1651

CA

HIS

A

213

−28.835

−46.715

0.132

1.00

108.71

A

C

ATOM

1652

CB

HIS

A

213

−29.208

−47.213

−1.272

1.00

108.63

A

C

ATOM

1653

CG

HIS

A

213

−29.145

−46.154

−2.331

1.00

108.64

A

C

ATOM

1654

ND1

HIS

A

213

−27.984

−45.841

−3.004

1.00

108.18

A

N

ATOM

1655

CE1

HIS

A

213

−28.225

−44.870

−3.866

1.00

108.50

A

C

ATOM

1656

NE2

HIS

A

213

−29.503

−44.547

−3.784

1.00

108.75

A

N

ATOM

1657

CD2

HIS

A

213

−30.102

−45.337

−2.833

1.00

108.68

A

C

ATOM

1658

C

HIS

A

213

−27.450

−46.116

0.113

1.00

109.12

A

C

ATOM

1659

O

HIS

A

213

−27.301

−44.902

−0.002

1.00

109.32

A

O

ATOM

1660

N

ALA

A

214

−26.443

−46.977

0.226

1.00

109.69

A

N

ATOM

1661

CA

ALA

A

214

−25.053

−46.583

0.053

1.00

110.09

A

C

ATOM

1662

CB

ALA

A

214

−24.131

−47.744

0.387

1.00

110.06

A

C

ATOM

1663

C

ALA

A

214

−24.865

−46.146

−1.387

1.00

110.39

A

C

ATOM

1664

O

ALA

A

214

−25.802

−46.185

−2.175

1.00

110.67

A

O

ATOM

1665

N

GLU

A

215

−23.664

−45.713

−1.732

1.00

110.82

A

N

ATOM

1666

CA

GLU

A

215

−23.376

−45.333

−3.098

1.00

111.51

A

C

ATOM

1667

CB

GLU

A

215

−22.167

−44.401

−3.148

1.00

111.88

A

C

ATOM

1668

CG

GLU

A

215

−22.260

−43.176

−2.216

1.00

114.33

A

C

ATOM

1669

CD

GLU

A

215

−21.817

−43.472

−0.777

1.00

117.27

A

C

ATOM

1670

OE1

GLU

A

215

−20.764

−42.939

−0.362

1.00

119.27

A

O

ATOM

1671

OE2

GLU

A

215

−22.507

−44.238

−0.063

1.00

117.73

A

O

ATOM

1672

C

GLU

A

215

−23.102

−46.620

−3.846

1.00

111.39

A

C

ATOM

1673

O

GLU

A

215

−22.531

−47.543

−3.276

1.00

111.69

A

O

ATOM

1674

N

TYR

A

216

−23.534

−46.709

−5.101

1.00

111.40

A

N

ATOM

1675

CA

TYR

A

216

−23.268

−47.907

−5.907

1.00

111.42

A

C

ATOM

1676

CB

TYR

A

216

−24.370

−48.958

−5.723

1.00

111.26

A

C

ATOM

1677

CG

TYR

A

216

−25.654

−48.586

−6.399

1.00

111.37

A

C

ATOM

1678

CD1

TYR

A

216

−25.891

−48.946

−7.725

1.00

111.76

A

C

ATOM

1679

CE1

TYR

A

216

−27.073

−48.592

−8.366

1.00

112.01

A

C

ATOM

1680

CZ

TYR

A

216

−28.033

−47.873

−7.675

1.00

111.92

A

C

ATOM

1681

OH

TYR

A

216

−29.200

−47.525

−8.307

1.00

112.07

A

O

ATOM

1682

CE2

TYR

A

216

−27.822

−47.504

−6.354

1.00

112.17

A

C

ATOM

1683

CD2

TYR

A

216

−26.631

−47.858

−5.725

1.00

111.63

A

C

ATOM

1684

C

TYR

A

216

−23.088

−47.598

−7.387

1.00

111.36

A

C

ATOM

1685

O

TYR

A

216

−23.651

−46.635

−7.902

1.00

111.49

A

O

ATOM

1686

N

THR

A

217

−22.324

−48.443

−8.068

1.00

111.37

A

N

ATOM

1687

CA

THR

A

217

−22.047

−48.265

−9.486

1.00

111.41

A

C

ATOM

1688

CB

THR

A

217

−20.726

−47.523

−9.694

1.00

111.32

A

C

ATOM

1689

OG1

THR

A

217

−20.949

−46.118

−9.536

1.00

111.25

A

O

ATOM

1690

CG2

THR

A

217

−20.171

−47.780

−11.077

1.00

111.13

A

C

ATOM

1691

C

THR

A

217

−22.036

−49.581

−10.251

1.00

111.65

A

C

ATOM

1692

O

THR

A

217

−21.378

−50.545

−9.858

1.00

111.68

A

O

ATOM

1693

N

LEU

A

218

−22.775

−49.607

−11.353

1.00

112.05

A

N

ATOM

1694

CA

LEU

A

218

−22.855

−50.790

−12.200

1.00

112.30

A

C

ATOM

1695

CB

LEU

A

218

−24.314

−51.237

−12.335

1.00

112.21

A

C

ATOM

1696

CG

LEU

A

218

−25.184

−51.254

−11.067

1.00

112.03

A

C

ATOM

1697

CD1

LEU

A

218

−26.585

−51.709

−11.388

1.00

112.90

A

C

ATOM

1698

CD2

LEU

A

218

−24.615

−52.153

−10.009

1.00

112.35

A

C

ATOM

1699

C

LEU

A

218

−22.236

−50.472

−13.558

1.00

112.47

A

C

ATOM

1700

O

LEU

A

218

−22.729

−49.597

−14.267

1.00

112.55

A

O

ATOM

1701

N

GLU

A

219

−21.153

−51.168

−13.903

1.00

112.67

A

N

ATOM

1702

CA

GLU

A

219

−20.351

−50.824

−15.081

1.00

113.16

A

C

ATOM

1703

CB

GLU

A

219

−18.926

−50.461

−14.672

1.00

113.15

A

C

ATOM

1704

CG

GLU

A

219

−18.785

−49.542

−13.481

1.00

113.45

A

C

ATOM

1705

CD

GLU

A

219

−17.333

−49.355

−13.067

1.00

113.68

A

C

ATOM

1706

OE1

GLU

A

219

−16.461

−50.073

−13.610

1.00

114.20

A

O

ATOM

1707

OE2

GLU

A

219

−17.062

−48.494

−12.200

1.00

113.06

A

O

ATOM

1708

C

GLU

A

219

−20.240

−51.934

−16.116

1.00

113.60

A

C

ATOM

1709

O

GLU

A

219

−20.418

−53.116

−15.804

1.00

113.73

A

O

ATOM

1710

N

ARG

A

220

−19.926

−51.543

−17.351

1.00

114.14

A

N

ATOM

1711

CA

ARG

A

220

−19.395

−52.486

−18.334

1.00

114.73

A

C

ATOM

1712

CB

ARG

A

220

−19.331

−51.879

−19.745

1.00

114.91

A

C

ATOM

1713

CG

ARG

A

220

−20.512

−52.208

−20.662

1.00

115.91

A

C

ATOM

1714

CD

ARG

A

220

−21.272

−50.947

−21.115

1.00

117.92

A

C

ATOM

1715

NE

ARG

A

220

−20.449

−50.069

−21.966

1.00

119.22

A

N

ATOM

1716

CZ

ARG

A

220

−20.883

−48.972

−22.595

1.00

119.15

A

C

ATOM

1717

NH1

ARG

A

220

−20.040

−48.260

−23.328

1.00

118.56

A

N

ATOM

1718

NH2

ARG

A

220

−22.150

−48.580

−22.499

1.00

119.31

A

N

ATOM

1719

C

ARG

A

220

−17.991

−52.875

−17.883

1.00

114.69

A

C

ATOM

1720

O

ARG

A

220

−17.226

−52.033

−17.408

1.00

114.74

A

O

ATOM

1721

N

GLY

A

221

−17.649

−54.149

−18.015

1.00

114.72

A

N

ATOM

1722

CA

GLY

A

221

−16.304

−54.576

−17.677

1.00

114.94

A

C

ATOM

1723

C

GLY

A

221

−16.045

−56.067

−17.632

1.00

115.22

A

C

ATOM

1724

O

GLY

A

221

−16.862

−56.859

−17.143

1.00

114.82

A

O

ATOM

1725

N

ASP

A

222

−14.891

−56.436

−18.181

1.00

115.53

A

N

ATOM

1726

CA

ASP

A

222

−14.304

−57.732

−17.940

1.00

115.67

A

C

ATOM

1727

CB

ASP

A

222

−13.484

−58.192

−19.137

1.00

115.52

A

C

ATOM

1728

CG

ASP

A

222

−13.171

−59.668

−19.083

1.00

116.10

A

C

ATOM

1729

OD1

ASP

A

222

−12.594

−60.118

−18.067

1.00

116.19

A

O

ATOM

1730

OD2

ASP

A

222

−13.503

−60.383

−20.057

1.00

116.68

A

O

ATOM

1731

C

ASP

A

222

−13.415

−57.489

−16.739

1.00

115.89

A

C

ATOM

1732

O

ASP

A

222

−12.617

−56.530

−16.726

1.00

116.09

A

O

ATOM

1733

N

PHE

A

223

−13.566

−58.315

−15.706

1.00

115.66

A

N

ATOM

1734

CA

PHE

A

223

−12.842

−58.023

−14.473

1.00

115.12

A

C

ATOM

1735

CB

PHE

A

223

−13.537

−58.563

−13.213

1.00

114.39

A

C

ATOM

1736

CG

PHE

A

223

−14.170

−59.914

−13.364

1.00

111.02

A

C

ATOM

1737

CD1

PHE

A

223

−13.397

−61.053

−13.480

1.00

108.84

A

C

ATOM

1738

CE1

PHE

A

223

−13.996

−62.300

−13.580

1.00

107.20

A

C

ATOM

1739

CZ

PHE

A

223

−15.376

−62.412

−13.540

1.00

105.58

A

C

ATOM

1740

CE2

PHE

A

223

−16.149

−61.295

−13.403

1.00

105.06

A

C

ATOM

1741

CD2

PHE

A

223

−15.549

−60.052

−13.307

1.00

108.11

A

C

ATOM

1742

C

PHE

A

223

−11.357

−58.366

−14.523

1.00

115.72

A

C

ATOM

1743

O

PHE

A

223

−10.563

−57.768

−13.798

1.00

115.89

A

O

ATOM

1744

N

LEU

A

224

−10.989

−59.297

−15.404

1.00

116.28

A

N

ATOM

1745

CA

LEU

A

224

−9.591

−59.678

−15.602

1.00

116.70

A

C

ATOM

1746

CB

LEU

A

224

−9.474

−60.876

−16.543

1.00

116.61

A

C

ATOM

1747

CG

LEU

A

224

−10.369

−62.108

−16.377

1.00

116.89

A

C

ATOM

1748

CD1

LEU

A

224

−10.136

−63.070

−17.529

1.00

117.22

A

C

ATOM

1749

CD2

LEU

A

224

−10.150

−62.818

−15.054

1.00

117.01

A

C

ATOM

1750

C

LEU

A

224

−8.764

−58.521

−16.153

1.00

117.22

A

C

ATOM

1751

O

LEU

A

224

−7.544

−58.505

−15.996

1.00

117.32

A

O

ATOM

1752

N

SER

A

225

−9.426

−57.550

−16.783

1.00

117.76

A

N

ATOM

1753

CA

SER

A

225

−8.736

−56.412

−17.395

1.00

118.40

A

C

ATOM

1754

CB

SER

A

225

−9.734

−55.385

−17.933

1.00

118.48

A

C

ATOM

1755

OG

SER

A

225

−10.294

−54.612

−16.884

1.00

118.97

A

O

ATOM

1756

C

SER

A

225

−7.716

−55.724

−16.484

1.00

118.70

A

C

ATOM

1757

O

SER

A

225

−7.829

−55.733

−15.256

1.00

118.76

A

O

ATOM

1758

N

GLU

A

226

−6.722

−55.128

−17.128

1.00

119.35

A

N

ATOM

1759

CA

GLU

A

226

−5.625

−54.399

−16.484

1.00

119.83

A

C

ATOM

1760

CB

GLU

A

226

−4.683

−53.794

−17.554

1.00

120.12

A

C

ATOM

1761

CG

GLU

A

226

−5.384

−53.174

−18.802

1.00

120.79

A

C

ATOM

1762

CD

GLU

A

226

−6.189

−54.195

−19.630

1.00

121.68

A

C

ATOM

1763

OE1

GLU

A

226

−5.692

−55.326

−19.852

1.00

121.37

A

O

ATOM

1764

OE2

GLU

A

226

−7.325

−53.864

−20.043

1.00

121.68

A

O

ATOM

1765

C

GLU

A

226

−6.080

−53.339

−15.471

1.00

119.63

A

C

ATOM

1766

O

GLU

A

226

−5.453

−53.170

−14.429

1.00

119.30

A

O

ATOM

1767

N

GLU

A

227

−7.170

−52.642

−15.778

1.00

119.81

A

N

ATOM

1768

CA

GLU

A

227

−7.722

−51.637

−14.865

1.00

120.24

A

C

ATOM

1769

CB

GLU

A

227

−8.847

−50.833

−15.539

1.00

120.25

A

C

ATOM

1770

CG

GLU

A

227

−9.402

−49.661

−14.711

1.00

120.07

A

C

ATOM

1771

CD

GLU

A

227

−10.862

−49.316

−15.050

1.00

120.33

A

C

ATOM

1772

OE1

GLU

A

227

−11.372

−48.288

−14.540

1.00

119.81

A

O

ATOM

1773

OE2

GLU

A

227

−11.504

−50.071

−15.821

1.00

119.75

A

O

ATOM

1774

C

GLU

A

227

−8.228

−52.288

−13.578

1.00

120.44

A

C

ATOM

1775

O

GLU

A

227

−7.964

−51.791

−12.480

1.00

120.51

A

O

ATOM

1776

N

TRP

A

228

−8.947

−53.401

−13.722

1.00

120.55

A

N

ATOM

1777

CA

TRP

A

228

−9.501

−54.107

−12.572

1.00

120.75

A

C

ATOM

1778

CB

TRP

A

228

−10.586

−55.114

−12.973

1.00

121.23

A

C

ATOM

1779

CG

TRP

A

228

−11.934

−54.460

−13.134

1.00

123.00

A

C

ATOM

1780

CD1

TRP

A

228

−12.587

−54.191

−14.306

1.00

124.02

A

C

ATOM

1781

NE1

TRP

A

228

−13.784

−53.560

−14.047

1.00

124.34

A

N

ATOM

1782

CE2

TRP

A

228

−13.920

−53.403

−12.692

1.00

124.56

A

C

ATOM

1783

CD2

TRP

A

228

−12.774

−53.956

−12.083

1.00

124.32

A

C

ATOM

1784

CE3

TRP

A

228

−12.671

−53.928

−10.686

1.00

124.96

A

C

ATOM

1785

CZ3

TRP

A

228

−13.704

−53.357

−9.949

1.00

125.13

A

C

ATOM

1786

CH2

TRP

A

228

−14.831

−52.819

−10.583

1.00

125.12

A

C

ATOM

1787

CZ2

TRP

A

228

−14.957

−52.829

−11.950

1.00

125.25

A

C

ATOM

1788

C

TRP

A

228

−8.433

−54.750

−11.717

1.00

120.30

A

C

ATOM

1789

O

TRP

A

228

−8.555

−54.738

−10.497

1.00

120.42

A

O

ATOM

1790

N

ARG

A

229

−7.384

−55.283

−12.344

1.00

119.89

A

N

ATOM

1791

CA

ARG

A

229

−6.187

−55.723

−11.608

1.00

119.57

A

C

ATOM

1792

CB

ARG

A

229

−4.927

−55.661

−12.487

1.00

119.57

A

C

ATOM

1793

CG

ARG

A

229

−4.898

−56.584

−13.684

1.00

119.56

A

C

ATOM

1794

CD

ARG

A

229

−3.468

−56.987

−14.029

1.00

119.51

A

C

ATOM

1795

NE

ARG

A

229

−3.128

−58.308

−13.499

1.00

120.11

A

N

ATOM

1796

CZ

ARG

A

229

−3.259

−59.449

−14.179

1.00

121.00

A

C

ATOM

1797

NH1

ARG

A

229

−3.715

−59.435

−15.423

1.00

121.68

A

N

ATOM

1798

NH2

ARG

A

229

−2.933

−60.615

−13.626

1.00

121.47

A

N

ATOM

1799

C

ARG

A

229

−5.945

−54.848

−10.371

1.00

119.20

A

C

ATOM

1800

O

ARG

A

229

−5.818

−55.357

−9.255

1.00

118.94

A

O

ATOM

1801

N

GLU

A

230

−5.902

−53.534

−10.602

1.00

118.85

A

N

ATOM

1802

CA

GLU

A

230

−5.614

−52.532

−9.574

1.00

118.67

A

C

ATOM

1803

CB

GLU

A

230

−5.223

−51.174

−10.199

1.00

118.91

A

C

ATOM

1804

CG

GLU

A

230

−4.362

−51.224

−11.465

1.00

120.28

A

C

ATOM

1805

CD

GLU

A

230

−2.876

−51.516

−11.207

1.00

122.49

A

C

ATOM

1806

OE1

GLU

A

230

−2.164

−50.640

−10.653

1.00

122.69

A

O

ATOM

1807

OE2

GLU

A

230

−2.414

−52.617

−11.596

1.00

122.89

A

O

ATOM

1808

C

GLU

A

230

−6.778

−52.313

−8.604

1.00

117.96

A

C

ATOM

1809

O

GLU

A

230

−6.552

−51.951

−7.448

1.00

118.21

A

O

ATOM

1810

N

ARG

A

231

−8.010

−52.508

−9.075

1.00

116.91

A

N

ATOM

1811

CA

ARG

A

231

−9.203

−52.244

−8.253

1.00

115.92

A

C

ATOM

1812

CB

ARG

A

231

−10.400

−51.884

−9.131

1.00

116.02

A

C

ATOM

1813

CG

ARG

A

231

−10.312

−50.492

−9.729

1.00

116.70

A

C

ATOM

1814

CD

ARG

A

231

−11.218

−50.343

−10.935

1.00

117.76

A

C

ATOM

1815

NE

ARG

A

231

−12.609

−50.092

−10.568

1.00

118.42

A

N

ATOM

1816

CZ

ARG

A

231

−13.560

−49.754

−11.434

1.00

118.53

A

C

ATOM

1817

NH1

ARG

A

231

−13.274

−49.626

−12.722

1.00

119.04

A

N

ATOM

1818

NH2

ARG

A

231

−14.799

−49.537

−11.016

1.00

118.29

A

N

ATOM

1819

C

ARG

A

231

−9.553

−53.389

−7.299

1.00

114.95

A

C

ATOM

1820

O

ARG

A

231

−9.796

−53.161

−6.111

1.00

114.70

A

O

ATOM

1821

N

ILE

A

232

−9.568

−54.610

−7.830

1.00

113.75

A

N

ATOM

1822

CA

ILE

A

232

−9.705

−55.831

−7.033

1.00

112.68

A

C

ATOM

1823

CB

ILE

A

232

−9.545

−57.086

−7.919

1.00

112.67

A

C

ATOM

1824

CG1

ILE

A

232

−10.384

−56.954

−9.190

1.00

112.94

A

C

ATOM

1825

CD1

ILE

A

232

−9.914

−57.833

−10.335

1.00

114.15

A

C

ATOM

1826

CG2

ILE

A

232

−9.920

−58.351

−7.164

1.00

112.12

A

C

ATOM

1827

C

ILE

A

232

−8.657

−55.873

−5.922

1.00

112.13

A

C

ATOM

1828

O

ILE

A

232

−8.865

−56.497

−4.885

1.00

111.89

A

O

ATOM

1829

N

ALA

A

233

−7.528

−55.207

−6.159

1.00

111.51

A

N

ATOM

1830

CA

ALA

A

233

−6.454

−55.097

−5.182

1.00

110.75

A

C

ATOM

1831

CB

ALA

A

233

−5.220

−54.518

−5.836

1.00

110.61

A

C

ATOM

1832

C

ALA

A

233

−6.872

−54.250

−3.974

1.00

110.25

A

C

ATOM

1833

O

ALA

A

233

−6.483

−54.537

−2.847

1.00

110.40

A

O

ATOM

1834

N

ASN

A

234

−7.673

−53.220

−4.208

1.00

109.39

A

N

ATOM

1835

CA

ASN

A

234

−8.085

−52.326

−3.136

1.00

108.78

A

C

ATOM

1836

CB

ASN

A

234

−8.043

−50.875

−3.626

1.00

108.67

A

C

ATOM

1837

CG

ASN

A

234

−6.632

−50.391

−3.902

0.50

108.15

A

C

ATOM

1838

OD1

ASN

A

234

−5.659

−50.948

−3.396

0.50

107.19

A

O

ATOM

1839

ND2

ASN

A

234

−6.517

−49.345

−4.709

0.50

107.96

A

N

ATOM

1840

C

ASN

A

234

−9.459

−52.649

−2.528

1.00

108.49

A

C

ATOM

1841

O

ASN

A

234

−9.963

−51.911

−1.677

1.00

108.49

A

O

ATOM

1842

N

THR

A

235

−10.051

−53.757

−2.959

1.00

107.91

A

N

ATOM

1843

CA

THR

A

235

−11.425

−54.102

−2.600

1.00

107.23

A

C

ATOM

1844

CB

THR

A

235

−12.174

−54.644

−3.829

1.00

107.20

A

C

ATOM

1845

OG1

THR

A

235

−11.853

−53.843

−4.968

1.00

106.64

A

O

ATOM

1846

CG2

THR

A

235

−13.668

−54.603

−3.617

1.00

107.79

A

C

ATOM

1847

C

THR

A

235

−11.435

−55.124

−1.463

1.00

106.91

A

C

ATOM

1848

O

THR

A

235

−10.683

−56.093

−1.485

1.00

107.01

A

O

ATOM

1849

N

SER

A

236

−12.293

−54.906

−0.476

1.00

106.42

A

N

ATOM

1850

CA

SER

A

236

−12.211

−55.631

0.792

1.00

105.96

A

C

ATOM

1851

CB

SER

A

236

−12.519

−54.672

1.947

1.00

106.28

A

C

ATOM

1852

OG

SER

A

236

−13.001

−55.358

3.088

1.00

107.19

A

O

ATOM

1853

C

SER

A

236

−13.113

−56.859

0.866

1.00

105.40

A

C

ATOM

1854

O

SER

A

236

−12.858

−57.788

1.636

1.00

105.47

A

O

ATOM

1855

N

VAL

A

237

−14.190

−56.852

0.097

1.00

104.60

A

N

ATOM

1856

CA

VAL

A

237

−15.082

−58.000

0.073

1.00

103.81

A

C

ATOM

1857

CB

VAL

A

237

−16.409

−57.752

0.828

1.00

103.91

A

C

ATOM

1858

CG1

VAL

A

237

−17.148

−59.082

1.053

1.00

103.44

A

C

ATOM

1859

CG2

VAL

A

237

−16.164

−57.036

2.162

1.00

104.04

A

C

ATOM

1860

C

VAL

A

237

−15.385

−58.321

−1.371

1.00

103.24

A

C

ATOM

1861

O

VAL

A

237

−15.569

−57.421

−2.198

1.00

103.51

A

O

ATOM

1862

N

ILE

A

238

−15.424

−59.606

−1.676

1.00

101.99

A

N

ATOM

1863

CA

ILE

A

238

−15.684

−60.028

−3.017

1.00

101.00

A

C

ATOM

1864

CB

ILE

A

238

−14.373

−60.420

−3.751

1.00

101.07

A

C

ATOM

1865

CG1

ILE

A

238

−13.500

−59.183

−3.978

1.00

100.77

A

C

ATOM

1866

CD1

ILE

A

238

−12.061

−59.496

−4.206

1.00

100.04

A

C

ATOM

1867

CG2

ILE

A

238

−14.668

−61.092

−5.096

1.00

101.02

A

C

ATOM

1868

C

ILE

A

238

−16.618

−61.201

−2.948

1.00

100.59

A

C

ATOM

1869

O

ILE

A

238

−16.253

−62.259

−2.433

1.00

100.74

A

O

ATOM

1870

N

PHE

A

239

−17.838

−60.990

−3.435

1.00

99.82

A

N

ATOM

1871

CA

PHE

A

239

−18.724

−62.078

−3.827

1.00

98.86

A

C

ATOM

1872

CB

PHE

A

239

−20.172

−61.618

−3.798

1.00

99.15

A

C

ATOM

1873

CG

PHE

A

239

−20.797

−61.598

−2.434

1.00

99.85

A

C

ATOM

1874

CD1

PHE

A

239

−20.127

−61.080

−1.340

1.00

100.49

A

C

ATOM

1875

CE1

PHE

A

239

−20.732

−61.043

−0.094

1.00

100.83

A

C

ATOM

1876

CZ

PHE

A

239

−22.019

−61.518

0.064

1.00

100.48

A

C

ATOM

1877

CE2

PHE

A

239

−22.703

−62.028

−1.020

1.00

99.75

A

C

ATOM

1878

CD2

PHE

A

239

−22.096

−62.058

−2.261

1.00

100.40

A

C

ATOM

1879

C

PHE

A

239

−18.364

−62.402

−5.263

1.00

97.99

A

C

ATOM

1880

O

PHE

A

239

−18.073

−61.501

−6.040

1.00

97.23

A

O

ATOM

1881

N

VAL

A

240

−18.382

−63.679

−5.620

1.00

97.63

A

N

ATOM

1882

CA

VAL

A

240

−18.044

−64.046

−6.977

1.00

97.59

A

C

ATOM

1883

CB

VAL

A

240

−16.608

−64.558

−7.094

1.00

97.61

A

C

ATOM

1884

CG1

VAL

A

240

−16.557

−66.055

−6.860

1.00

97.87

A

C

ATOM

1885

CG2

VAL

A

240

−16.042

−64.192

−8.460

1.00

97.17

A

C

ATOM

1886

C

VAL

A

240

−19.035

−64.959

−7.693

1.00

97.64

A

C

ATOM

1887

O

VAL

A

240

−19.608

−64.563

−8.710

1.00

98.21

A

O

ATOM

1888

N

ASN

A

241

−19.250

−66.160

−7.167

1.00

97.27

A

N

ATOM

1889

CA

ASN

A

241

−19.978

−67.224

−7.895

1.00

97.51

A

C

ATOM

1890

CB

ASN

A

241

−21.473

−66.932

−8.163

1.00

96.79

A

C

ATOM

1891

CG

ASN

A

241

−22.260

−68.208

−8.526

1.00

95.57

A

C

ATOM

1892

OD1

ASN

A

241

−21.746

−69.314

−8.410

1.00

94.21

A

O

ATOM

1893

ND2

ASN

A

241

−23.500

−68.050

−8.961

1.00

94.27

A

N

ATOM

1894

C

ASN

A

241

−19.281

−67.681

−9.174

1.00

98.24

A

C

ATOM

1895

O

ASN

A

241

−19.688

−67.348

−10.294

1.00

98.06

A

O

ATOM

1896

N

ASN

A

242

−18.211

−68.440

−8.969

1.00

99.17

A

N

ATOM

1897

CA

ASN

A

242

−17.515

−69.136

−10.025

1.00

99.66

A

C

ATOM

1898

CB

ASN

A

242

−16.093

−69.473

−9.569

1.00

99.43

A

C

ATOM

1899

CG

ASN

A

242

−15.998

−69.808

−8.070

1.00

99.04

A

C

ATOM

1900

OD1

ASN

A

242

−17.002

−69.978

−7.376

1.00

97.86

A

O

ATOM

1901

ND2

ASN

A

242

−14.773

−69.915

−7.578

1.00

98.94

A

N

ATOM

1902

C

ASN

A

242

−18.341

−70.376

−10.391

1.00

100.57

A

C

ATOM

1903

O

ASN

A

242

−19.414

−70.250

−10.989

1.00

100.63

A

O

ATOM

1904

N

PHE

A

243

−17.872

−71.561

−10.016

1.00

101.69

A

N

ATOM

1905

CA

PHE

A

243

−18.667

−72.787

−10.145

1.00

102.99

A

C

ATOM

1906

CB

PHE

A

243

−20.121

−72.592

−9.669

1.00

103.22

A

C

ATOM

1907

CG

PHE

A

243

−20.954

−73.840

−9.768

1.00

105.17

A

C

ATOM

1908

CD1

PHE

A

243

−20.694

−74.937

−8.932

1.00

106.83

A

C

ATOM

1909

CE1

PHE

A

243

−21.444

−76.110

−9.026

1.00

106.94

A

C

ATOM

1910

CZ

PHE

A

243

−22.466

−76.193

−9.957

1.00

107.70

A

C

ATOM

1911

CE2

PHE

A

243

−22.736

−75.100

−10.803

1.00

107.37

A

C

ATOM

1912

CD2

PHE

A

243

−21.977

−73.938

−10.705

1.00

106.12

A

C

ATOM

1913

C

PHE

A

243

−18.639

−73.365

−11.555

1.00

103.27

A

C

ATOM

1914

O

PHE

A

243

−18.285

−74.532

−11.753

1.00

103.68

A

O

ATOM

1915

N

ALA

A

244

−19.070

−72.561

−12.517

1.00

103.38

A

N

ATOM

1916

CA

ALA

A

244

−18.856

−72.841

−13.917

1.00

103.23

A

C

ATOM

1917

CB

ALA

A

244

−20.153

−72.723

−14.690

1.00

103.20

A

C

ATOM

1918

C

ALA

A

244

−17.899

−71.754

−14.327

1.00

103.25

A

C

ATOM

1919

O

ALA

A

244

−18.327

−70.671

−14.741

1.00

103.62

A

O

ATOM

1920

N

PHE

A

245

−16.608

−72.015

−14.158

1.00

103.07

A

N

ATOM

1921

CA

PHE

A

245

−15.598

−71.039

−14.540

1.00

103.15

A

C

ATOM

1922

CB

PHE

A

245

−15.178

−70.181

−13.339

1.00

103.00

A

C

ATOM

1923

CG

PHE

A

245

−15.802

−68.799

−13.327

1.00

102.41

A

C

ATOM

1924

CD1

PHE

A

245

−16.951

−68.519

−14.060

1.00

102.33

A

C

ATOM

1925

CE1

PHE

A

245

−17.528

−67.238

−14.045

1.00

103.08

A

C

ATOM

1926

CZ

PHE

A

245

−16.952

−66.226

−13.289

1.00

101.82

A

C

ATOM

1927

CE2

PHE

A

245

−15.815

−66.497

−12.548

1.00

101.84

A

C

ATOM

1928

CD2

PHE

A

245

−15.245

−67.780

−12.568

1.00

102.06

A

C

ATOM

1929

C

PHE

A

245

−14.403

−71.630

−15.274

1.00

103.35

A

C

ATOM

1930

O

PHE

A

245

−13.838

−70.987

−16.149

1.00

103.36

A

O

ATOM

1931

N

GLY

A

246

−14.030

−72.855

−14.939

1.00

103.91

A

N

ATOM

1932

CA

GLY

A

246

−12.918

−73.508

−15.609

1.00

104.92

A

C

ATOM

1933

C

GLY

A

246

−11.549

−72.876

−15.361

1.00

105.95

A

C

ATOM

1934

O

GLY

A

246

−11.396

−71.641

−15.391

1.00

106.04

A

O

ATOM

1935

N

PRO

A

247

−10.537

−73.730

−15.139

1.00

106.43

A

N

ATOM

1936

CA

PRO

A

247

−9.134

−73.520

−14.827

1.00

107.04

A

C

ATOM

1937

CB

PRO

A

247

−8.447

−74.623

−15.635

1.00

107.03

A

C

ATOM

1938

CG

PRO

A

247

−9.522

−75.691

−15.846

1.00

106.95

A

C

ATOM

1939

CD

PRO

A

247

−10.809

−75.168

−15.268

1.00

106.59

A

C

ATOM

1940

C

PRO

A

247

−8.504

−72.161

−15.149

1.00

107.78

A

C

ATOM

1941

O

PRO

A

247

−7.877

−71.566

−14.266

1.00

108.03

A

O

ATOM

1942

N

GLU

A

248

−8.624

−71.673

−16.379

1.00

108.51

A

N

ATOM

1943

CA

GLU

A

248

−7.875

−70.462

−16.732

1.00

109.43

A

C

ATOM

1944

CB

GLU

A

248

−7.908

−70.157

−18.241

1.00

109.61

A

C

ATOM

1945

CG

GLU

A

248

−6.790

−69.192

−18.684

1.00

109.52

A

C

ATOM

1946

CD

GLU

A

248

−6.639

−69.077

−20.186

0.50

109.38

A

C

ATOM

1947

OE1

GLU

A

248

−6.384

−70.105

−20.850

0.50

109.55

A

O

ATOM

1948

OE2

GLU

A

248

−6.753

−67.946

−20.699

0.50

109.25

A

O

ATOM

1949

C

GLU

A

248

−8.332

−69.253

−15.909

1.00

109.87

A

C

ATOM

1950

O

GLU

A

248

−7.512

−68.592

−15.254

1.00

109.61

A

O

ATOM

1951

N

VAL

A

249

−9.640

−68.989

−15.933

1.00

110.47

A

N

ATOM

1952

CA

VAL

A

249

−10.215

−67.855

−15.204

1.00

110.84

A

C

ATOM

1953

CB

VAL

A

249

−11.745

−67.691

−15.443

1.00

110.79

A

C

ATOM

1954

CG1

VAL

A

249

−12.204

−66.339

−14.946

1.00

110.58

A

C

ATOM

1955

CG2

VAL

A

249

−12.110

−67.849

−16.923

1.00

110.96

A

C

ATOM

1956

C

VAL

A

249

−9.941

−68.034

−13.717

1.00

111.09

A

C

ATOM

1957

O

VAL

A

249

−9.453

−67.112

−13.059

1.00

111.13

A

O

ATOM

1958

N

ASP

A

250

−10.241

−69.239

−13.222

1.00

111.33

A

N

ATOM

1959

CA

ASP

A

250

−10.024

−69.658

−11.833

1.00

111.47

A

C

ATOM

1960

CB

ASP

A

250

−10.138

−71.176

−11.752

1.00

111.92

A

C

ATOM

1961

CG

ASP

A

250

−10.600

−71.661

−10.394

1.00

113.98

A

C

ATOM

1962

OD1

ASP

A

250

−10.206

−71.070

−9.360

1.00

115.46

A

O

ATOM

1963

OD2

ASP

A

250

−11.364

−72.654

−10.369

1.00

116.45

A

O

ATOM

1964

C

ASP

A

250

−8.663

−69.235

−11.305

1.00

110.98

A

C

ATOM

1965

O

ASP

A

250

−8.560

−68.570

−10.281

1.00

110.69

A

O

ATOM

1966

N

HIS

A

251

−7.626

−69.650

−12.021

1.00

110.88

A

N

ATOM

1967

CA

HIS

A

251

−6.255

−69.219

−11.785

1.00

110.80

A

C

ATOM

1968

CB

HIS

A

251

−5.349

−69.900

−12.822

1.00

110.91

A

C

ATOM

1969

CG

HIS

A

251

−3.968

−69.329

−12.919

1.00

110.51

A

C

ATOM

1970

ND1

HIS

A

251

−2.839

−70.112

−12.831

1.00

110.48

A

N

ATOM

1971

CE1

HIS

A

251

−1.768

−69.352

−12.969

1.00

111.11

A

C

ATOM

1972

NE2

HIS

A

251

−2.162

−68.103

−13.146

1.00

110.98

A

N

ATOM

1973

CD2

HIS

A

251

−3.534

−68.063

−13.132

1.00

110.25

A

C

ATOM

1974

C

HIS

A

251

−6.152

−67.692

−11.870

1.00

110.65

A

C

ATOM

1975

O

HIS

A

251

−5.762

−67.030

−10.909

1.00

110.55

A

O

ATOM

1976

N

GLN

A

252

−6.522

−67.137

−13.018

1.00

110.52

A

N

ATOM

1977

CA

GLN

A

252

−6.393

−65.705

−13.243

1.00

110.47

A

C

ATOM

1978

CB

GLN

A

252

−7.061

−65.296

−14.553

1.00

110.92

A

C

ATOM

1979

CG

GLN

A

252

−6.313

−65.695

−15.821

1.00

112.07

A

C

ATOM

1980

CD

GLN

A

252

−7.147

−65.437

−17.066

1.00

113.66

A

C

ATOM

1981

OE1

GLN

A

252

−7.908

−66.308

−17.515

1.00

113.98

A

O

ATOM

1982

NE2

GLN

A

252

−7.033

−64.228

−17.613

1.00

113.20

A

N

ATOM

1983

C

GLN

A

252

−6.969

−64.889

−12.095

1.00

109.95

A

C

ATOM

1984

O

GLN

A

252

−6.453

−63.821

−11.792

1.00

110.05

A

O

ATOM

1985

N

LEU

A

253

−8.032

−65.400

−11.467

1.00

109.32

A

N

ATOM

1986

CA

LEU

A

253

−8.679

−64.741

−10.325

1.00

108.43

A

C

ATOM

1987

CB

LEU

A

253

−9.981

−65.450

−9.960

1.00

108.22

A

C

ATOM

1988

CG

LEU

A

253

−11.209

−65.297

−10.852

1.00

107.98

A

C

ATOM

1989

CD1

LEU

A

253

−12.205

−66.389

−10.543

1.00

107.33

A

C

ATOM

1990

CD2

LEU

A

253

−11.866

−63.926

−10.720

1.00

107.70

A

C

ATOM

1991

C

LEU

A

253

−7.763

−64.730

−9.112

1.00

108.05

A

C

ATOM

1992

O

LEU

A

253

−7.494

−63.676

−8.527

1.00

107.71

A

O

ATOM

1993

N

LYS

A

254

−7.286

−65.917

−8.746

1.00

107.72

A

N

ATOM

1994

CA

LYS

A

254

−6.353

−66.068

−7.650

1.00

107.63

A

C

ATOM

1995

CB

LYS

A

254

−5.772

−67.476

−7.621

1.00

107.29

A

C

ATOM

1996

CG

LYS

A

254

−6.791

−68.555

−7.383

1.00

105.91

A

C

ATOM

1997

CD

LYS

A

254

−6.310

−69.871

−7.925

1.00

103.89

A

C

ATOM

1998

CE

LYS

A

254

−7.397

−70.893

−7.805

1.00

103.55

A

C

ATOM

1999

NZ

LYS

A

254

−7.154

−72.105

−8.632

1.00

103.97

A

N

ATOM

2000

C

LYS

A

254

−5.238

−65.049

−7.803

1.00

108.18

A

C

ATOM

2001

O

LYS

A

254

−4.843

−64.406

−6.832

1.00

108.47

A

O

ATOM

2002

N

GLU

A

255

−4.751

−64.875

−9.027

1.00

108.48

A

N

ATOM

2003

CA

GLU

A

255

−3.692

−63.908

−9.267

1.00

108.88

A

C

ATOM

2004

CB

GLU

A

255

−3.396

−63.757

−10.756

1.00

108.95

A

C

ATOM

2005

CG

GLU

A

255

−2.465

−64.839

−11.280

1.00

109.64

A

C

ATOM

2006

CD

GLU

A

255

−1.189

−64.277

−11.872

1.00

110.14

A

C

ATOM

2007

OE1

GLU

A

255

−1.124

−63.042

−12.119

1.00

110.31

A

O

ATOM

2008

OE2

GLU

A

255

−0.252

−65.080

−12.080

1.00

109.80

A

O

ATOM

2009

C

GLU

A

255

−4.001

−62.557

−8.647

1.00

108.97

A

C

ATOM

2010

O

GLU

A

255

−3.157

−61.984

−7.955

1.00

109.15

A

O

ATOM

2011

N

ARG

A

256

−5.216

−62.064

−8.873

1.00

108.96

A

N

ATOM

2012

CA

ARG

A

256

−5.604

−60.764

−8.351

1.00

108.98

A

C

ATOM

2013

CB

ARG

A

256

−6.841

−60.239

−9.057

1.00

109.13

A

C

ATOM

2014

CG

ARG

A

256

−6.580

−59.713

−10.441

1.00

109.10

A

C

ATOM

2015

CD

ARG

A

256

−6.676

−60.821

−11.428

1.00

108.89

A

C

ATOM

2016

NE

ARG

A

256

−6.662

−60.302

−12.778

1.00

110.08

A

N

ATOM

2017

CZ

ARG

A

256

−6.262

−60.995

−13.834

1.00

111.25

A

C

ATOM

2018

NH1

ARG

A

256

−5.832

−62.245

−13.705

1.00

111.41

A

N

ATOM

2019

NH2

ARG

A

256

−6.287

−60.427

−15.024

1.00

112.41

A

N

ATOM

2020

C

ARG

A

256

−5.851

−60.807

−6.863

1.00

108.93

A

C

ATOM

2021

O

ARG

A

256

−5.402

−59.926

−6.141

1.00

108.68

A

O

ATOM

2022

N

PHE

A

257

−6.563

−61.839

−6.417

1.00

109.20

A

N

ATOM

2023

CA

PHE

A

257

−6.815

−62.051

−4.994

1.00

109.50

A

C

ATOM

2024

CB

PHE

A

257

−7.586

−63.345

−4.766

1.00

109.07

A

C

ATOM

2025

CG

PHE

A

257

−8.921

−63.389

−5.438

1.00

107.98

A

C

ATOM

2026

CD1

PHE

A

257

−9.706

−62.258

−5.541

1.00

107.26

A

C

ATOM

2027

CE1

PHE

A

257

−10.950

−62.318

−6.170

1.00

107.15

A

C

ATOM

2028

CZ

PHE

A

257

−11.419

−63.518

−6.675

1.00

106.38

A

C

ATOM

2029

CE2

PHE

A

257

−10.652

−64.654

−6.558

1.00

106.72

A

C

ATOM

2030

CD2

PHE

A

257

−9.411

−64.587

−5.940

1.00

107.81

A

C

ATOM

2031

C

PHE

A

257

−5.516

−62.083

−4.182

1.00

110.15

A

C

ATOM

2032

O

PHE

A

257

−5.462

−61.578

−3.054

1.00

110.32

A

O

ATOM

2033

N

ALA

A

258

−4.473

−62.672

−4.768

1.00

110.63

A

N

ATOM

2034

CA

ALA

A

258

−3.152

−62.733

−4.145

1.00

110.94

A

C

ATOM

2035

CB

ALA

A

258

−2.172

−63.467

−5.043

1.00

110.79

A

C

ATOM

2036

C

ALA

A

258

−2.625

−61.349

−3.816

1.00

111.19

A

C

ATOM

2037

O

ALA

A

258

−1.901

−61.180

−2.843

1.00

111.46

A

O

ATOM

2038

N

ASN

A

259

−2.992

−60.366

−4.632

1.00

111.49

A

N

ATOM

2039

CA

ASN

A

259

−2.481

−59.012

−4.476

1.00

111.88

A

C

ATOM

2040

CB

ASN

A

259

−2.560

−58.251

−5.806

1.00

111.79

A

C

ATOM

2041

CG

ASN

A

259

−1.234

−58.216

−6.549

1.00

111.91

A

C

ATOM

2042

OD1

ASN

A

259

−0.601

−59.251

−6.793

1.00

111.54

A

O

ATOM

2043

ND2

ASN

A

259

−0.812

−57.014

−6.926

1.00

111.97

A

N

ATOM

2044

C

ASN

A

259

−3.229

−58.250

−3.404

1.00

112.15

A

C

ATOM

2045

O

ASN

A

259

−2.871

−57.121

−3.085

1.00

112.24

A

O

ATOM

2046

N

MET

A

260

−4.263

−58.880

−2.849

1.00

112.58

A

N

ATOM

2047

CA

MET

A

260

−5.232

−58.193

−1.993

1.00

112.90

A

C

ATOM

2048

CB

MET

A

260

−6.486

−59.044

−1.812

1.00

112.95

A

C

ATOM

2049

CG

MET

A

260

−7.445

−59.000

−2.990

1.00

113.05

A

C

ATOM

2050

SD

MET

A

260

−8.920

−59.984

−2.687

1.00

113.36

A

S

ATOM

2051

CE

MET

A

260

−9.687

−59.025

−1.382

1.00

111.63

A

C

ATOM

2052

C

MET

A

260

−4.689

−57.830

−0.631

1.00

113.06

A

C

ATOM

2053

O

MET

A

260

−3.924

−58.588

−0.037

1.00

112.94

A

O

ATOM

2054

N

LYS

A

261

−5.110

−56.673

−0.133

1.00

113.38

A

N

ATOM

2055

CA

LYS

A

261

−4.741

−56.249

1.206

1.00

113.95

A

C

ATOM

2056

CB

LYS

A

261

−5.263

−54.843

1.506

1.00

114.21

A

C

ATOM

2057

CG

LYS

A

261

−4.245

−53.722

1.242

1.00

115.28

A

C

ATOM

2058

CD

LYS

A

261

−4.332

−53.174

−0.181

1.00

116.47

A

C

ATOM

2059

CE

LYS

A

261

−3.575

−51.862

−0.303

1.00

117.59

A

C

ATOM

2060

NZ

LYS

A

261

−4.190

−50.945

−1.312

1.00

118.31

A

N

ATOM

2061

C

LYS

A

261

−5.220

−57.240

2.262

1.00

113.99

A

C

ATOM

2062

O

LYS

A

261

−6.048

−58.115

1.988

1.00

114.41

A

O

ATOM

2063

N

GLU

A

262

−4.674

−57.104

3.466

1.00

113.73

A

N

ATOM

2064

CA

GLU

A

262

−4.925

−58.032

4.558

1.00

113.21

A

C

ATOM

2065

CB

GLU

A

262

−4.130

−57.577

5.791

1.00

113.51

A

C

ATOM

2066

CG

GLU

A

262

−3.329

−58.672

6.509

1.00

113.70

A

C

ATOM

2067

CD

GLU

A

262

−4.195

−59.618

7.342

1.00

113.53

A

C

ATOM

2068

OE1

GLU

A

262

−3.667

−60.684

7.747

1.00

113.85

A

O

ATOM

2069

OE2

GLU

A

262

−5.386

−59.302

7.587

1.00

111.65

A

O

ATOM

2070

C

GLU

A

262

−6.415

−58.090

4.883

1.00

112.63

A

C

ATOM

2071

O

GLU

A

262

−7.132

−57.105

4.702

1.00

112.47

A

O

ATOM

2072

N

GLY

A

263

−6.875

−59.255

5.329

1.00

112.01

A

N

ATOM

2073

CA

GLY

A

263

−8.212

−59.410

5.920

1.00

111.42

A

C

ATOM

2074

C

GLY

A

263

−9.468

−59.128

5.098

1.00

110.87

A

C

ATOM

2075

O

GLY

A

263

−10.584

−59.164

5.643

1.00

111.04

A

O

ATOM

2076

N

GLY

A

264

−9.303

−58.838

3.807

1.00

110.02

A

N

ATOM

2077

CA

GLY

A

264

−10.440

−58.710

2.898

1.00

108.89

A

C

ATOM

2078

C

GLY

A

264

−11.012

−60.079

2.565

1.00

108.24

A

C

ATOM

2079

O

GLY

A

264

−10.278

−60.967

2.148

1.00

108.13

A

O

ATOM

2080

N

ARG

A

265

−12.317

−60.264

2.752

1.00

107.57

A

N

ATOM

2081

CA

ARG

A

265

−12.914

−61.590

2.543

1.00

106.93

A

C

ATOM

2082

CB

ARG

A

265

−14.126

−61.844

3.448

1.00

106.92

A

C

ATOM

2083

CG

ARG

A

265

−13.970

−61.538

4.925

1.00

107.03

A

C

ATOM

2084

CD

ARG

A

265

−14.658

−60.239

5.291

1.00

106.92

A

C

ATOM

2085

NE

ARG

A

265

−13.724

−59.122

5.282

1.00

108.09

A

N

ATOM

2086

CZ

ARG

A

265

−14.075

−57.849

5.428

1.00

109.50

A

C

ATOM

2087

NH1

ARG

A

265

−15.352

−57.516

5.579

1.00

110.29

A

N

ATOM

2088

NH2

ARG

A

265

−13.148

−56.902

5.424

1.00

109.90

A

N

ATOM

2089

C

ARG

A

265

−13.333

−61.816

1.095

1.00

106.40

A

C

ATOM

2090

O

ARG

A

265

−13.480

−60.858

0.325

1.00

106.31

A

O

ATOM

2091

N

ILE

A

266

−13.519

−63.092

0.750

1.00

105.47

A

N

ATOM

2092

CA

ILE

A

266

−14.006

−63.514

−0.551

1.00

104.83

A

C

ATOM

2093

CB

ILE

A

266

−12.905

−64.190

−1.439

1.00

104.80

A

C

ATOM

2094

CG1

ILE

A

266

−11.475

−63.687

−1.138

1.00

104.82

A

C

ATOM

2095

CD1

ILE

A

266

−11.101

−62.325

−1.680

1.00

104.47

A

C

ATOM

2096

CG2

ILE

A

266

−13.306

−64.187

−2.940

1.00

104.09

A

C

ATOM

2097

C

ILE

A

266

−15.027

−64.605

−0.308

1.00

104.85

A

C

ATOM

2098

O

ILE

A

266

−14.697

−65.648

0.261

1.00

105.00

A

O

ATOM

2099

N

VAL

A

267

−16.264

−64.383

−0.749

1.00

104.76

A

N

ATOM

2100

CA

VAL

A

267

−17.272

−65.451

−0.763

1.00

104.35

A

C

ATOM

2101

CB

VAL

A

267

−18.613

−65.033

−0.125

1.00

104.37

A

C

ATOM

2102

CG1

VAL

A

267

−19.201

−66.199

0.629

1.00

103.94

A

C

ATOM

2103

CG2

VAL

A

267

−18.435

−63.868

0.808

1.00

104.08

A

C

ATOM

2104

C

VAL

A

267

−17.511

−65.935

−2.195

1.00

104.20

A

C

ATOM

2105

O

VAL

A

267

−17.582

−65.142

−3.127

1.00

103.93

A

O

ATOM

2106

N

SER

A

268

−17.649

−67.245

−2.350

1.00

104.26

A

N

ATOM

2107

CA

SER

A

268

−17.607

−67.873

−3.651

1.00

104.44

A

C

ATOM

2108

CB

SER

A

268

−16.146

−68.082

−4.047

1.00

104.55

A

C

ATOM

2109

OG

SER

A

268

−15.540

−69.087

−3.255

1.00

104.04

A

O

ATOM

2110

C

SER

A

268

−18.310

−69.222

−3.644

1.00

104.74

A

C

ATOM

2111

O

SER

A

268

−18.233

−69.965

−2.667

1.00

104.60

A

O

ATOM

2112

N

SER

A

269

−18.973

−69.539

−4.753

1.00

105.26

A

N

ATOM

2113

CA

SER

A

269

−19.614

−70.839

−4.938

1.00

105.59

A

C

ATOM

2114

CB

SER

A

269

−20.327

−70.902

−6.282

1.00

105.51

A

C

ATOM

2115

OG

SER

A

269

−19.484

−70.459

−7.324

1.00

105.14

A

O

ATOM

2116

C

SER

A

269

−18.607

−71.970

−4.851

1.00

105.99

A

C

ATOM

2117

O

SER

A

269

−18.874

−72.977

−4.198

1.00

106.11

A

O

ATOM

2118

N

LYS

A

270

−17.462

−71.790

−5.514

1.00

106.39

A

N

ATOM

2119

CA

LYS

A

270

−16.362

−72.754

−5.503

1.00

106.78

A

C

ATOM

2120

CB

LYS

A

270

−15.894

−73.047

−6.929

1.00

106.99

A

C

ATOM

2121

CG

LYS

A

270

−16.644

−74.158

−7.657

1.00

107.91

A

C

ATOM

2122

CD

LYS

A

270

−15.912

−74.531

−8.951

1.00

109.06

A

C

ATOM

2123

CE

LYS

A

270

−16.323

−75.902

−9.500

1.00

109.35

A

C

ATOM

2124

NZ

LYS

A

270

−15.228

−76.492

−10.339

1.00

109.13

A

N

ATOM

2125

C

LYS

A

270

−15.185

−72.220

−4.689

1.00

106.90

A

C

ATOM

2126

O

LYS

A

270

−15.010

−71.008

−4.579

1.00

106.68

A

O

ATOM

2127

N

PRO

A

271

−14.364

−73.124

−4.120

1.00

107.20

A

N

ATOM

2128

CA

PRO

A

271

−13.221

−72.655

−3.348

1.00

107.62

A

C

ATOM

2129

CB

PRO

A

271

−13.003

−73.782

−2.334

1.00

107.49

A

C

ATOM

2130

CG

PRO

A

271

−13.523

−75.012

−2.996

1.00

106.82

A

C

ATOM

2131

CD

PRO

A

271

−14.504

−74.592

−4.063

1.00

107.18

A

C

ATOM

2132

C

PRO

A

271

−11.962

−72.428

−4.193

1.00

108.37

A

C

ATOM

2133

O

PRO

A

271

−11.557

−73.290

−4.982

1.00

108.36

A

O

ATOM

2134

N

PHE

A

272

−11.350

−71.263

−4.018

1.00

109.24

A

N

ATOM

2135

CA

PHE

A

272

−10.076

−70.963

−4.653

1.00

110.07

A

C

ATOM

2136

CB

PHE

A

272

−9.864

−69.457

−4.717

1.00

110.18

A

C

ATOM

2137

CG

PHE

A

272

−10.864

−68.752

−5.574

1.00

110.21

A

C

ATOM

2138

CD1

PHE

A

272

−10.802

−68.847

−6.950

1.00

110.61

A

C

ATOM

2139

CE1

PHE

A

272

−11.727

−68.211

−7.742

1.00

110.94

A

C

ATOM

2140

CZ

PHE

A

272

−12.730

−67.465

−7.165

1.00

111.46

A

C

ATOM

2141

CE2

PHE

A

272

−12.810

−67.369

−5.793

1.00

111.56

A

C

ATOM

2142

CD2

PHE

A

272

−11.877

−68.012

−5.005

1.00

111.07

A

C

ATOM

2143

C

PHE

A

272

−8.909

−71.644

−3.948

1.00

110.85

A

C

ATOM

2144

O

PHE

A

272

−7.866

−71.868

−4.557

1.00

111.20

A

O

ATOM

2145

N

ALA

A

273

−9.087

−71.958

−2.666

1.00

111.82

A

N

ATOM

2146

CA

ALA

A

273

−8.163

−72.815

−1.918

1.00

112.52

A

C

ATOM

2147

CB

ALA

A

273

−7.500

−72.039

−0.817

1.00

112.37

A

C

ATOM

2148

C

ALA

A

273

−8.918

−73.998

−1.334

1.00

113.25

A

C

ATOM

2149

O

ALA

A

273

−10.091

−73.858

−0.987

1.00

113.34

A

O

ATOM

2150

N

PRO

A

274

−8.259

−75.170

−1.236

1.00

114.11

A

N

ATOM

2151

CA

PRO

A

274

−8.782

−76.342

−0.513

1.00

114.94

A

C

ATOM

2152

CB

PRO

A

274

−7.663

−77.371

−0.685

1.00

114.66

A

C

ATOM

2153

CG

PRO

A

274

−7.065

−77.023

−1.985

1.00

114.18

A

C

ATOM

2154

CD

PRO

A

274

−7.076

−75.526

−2.040

1.00

114.03

A

C

ATOM

2155

C

PRO

A

274

−9.069

−76.123

0.990

1.00

115.88

A

C

ATOM

2156

O

PRO

A

274

−8.667

−75.113

1.580

1.00

115.88

A

O

ATOM

2157

N

LEU

A

275

−9.763

−77.079

1.595

1.00

117.10

A

N

ATOM

2158

CA

LEU

A

275

−10.088

−77.016

3.017

1.00

118.37

A

C

ATOM

2159

CB

LEU

A

275

−11.482

−77.602

3.282

1.00

118.36

A

C

ATOM

2160

CG

LEU

A

275

−12.669

−76.782

2.763

1.00

117.65

A

C

ATOM

2161

CD1

LEU

A

275

−13.857

−77.672

2.480

1.00

116.90

A

C

ATOM

2162

CD2

LEU

A

275

−13.026

−75.675

3.739

1.00

116.83

A

C

ATOM

2163

C

LEU

A

275

−9.038

−77.727

3.857

1.00

119.34

A

C

ATOM

2164

O

LEU

A

275

−8.509

−77.149

4.803

1.00

119.32

A

O

ATOM

2165

N

ASN

A

276

−8.740

−78.977

3.499

1.00

120.77

A

N

ATOM

2166

CA

ASN

A

276

−7.666

−79.742

4.149

1.00

122.27

A

C

ATOM

2167

CB

ASN

A

276

−7.823

−81.276

3.931

1.00

122.62

A

C

ATOM

2168

CG

ASN

A

276

−7.835

−81.699

2.440

1.00

123.52

A

C

ATOM

2169

OD1

ASN

A

276

−7.195

−81.081

1.586

1.00

124.43

A

O

ATOM

2170

ND2

ASN

A

276

−8.556

−82.782

2.143

1.00

123.75

A

N

ATOM

2171

C

ASN

A

276

−6.258

−79.257

3.775

1.00

122.82

A

C

ATOM

2172

O

ASN

A

276

−5.400

−80.056

3.386

1.00

122.72

A

O

ATOM

2173

N

PHE

A

277

−6.027

−77.951

3.917

1.00

123.71

A

N

ATOM

2174

CA

PHE

A

277

−4.778

−77.337

3.472

1.00

124.86

A

C

ATOM

2175

CB

PHE

A

277

−5.056

−76.081

2.638

1.00

124.98

A

C

ATOM

2176

CG

PHE

A

277

−3.815

−75.448

2.035

1.00

125.69

A

C

ATOM

2177

CD1

PHE

A

277

−3.158

−76.046

0.958

1.00

125.82

A

C

ATOM

2178

CE1

PHE

A

277

−2.025

−75.462

0.395

1.00

125.79

A

C

ATOM

2179

CZ

PHE

A

277

−1.539

−74.261

0.897

1.00

126.00

A

C

ATOM

2180

CE2

PHE

A

277

−2.184

−73.648

1.963

1.00

126.13

A

C

ATOM

2181

CD2

PHE

A

277

−3.321

−74.240

2.526

1.00

126.09

A

C

ATOM

2182

C

PHE

A

277

−3.808

−77.023

4.606

1.00

125.54

A

C

ATOM

2183

O

PHE

A

277

−3.887

−75.958

5.231

1.00

125.72

A

O

ATOM

2184

N

ARG

A

278

−2.903

−77.966

4.864

1.00

126.29

A

N

ATOM

2185

CA

ARG

A

278

−1.737

−77.727

5.706

1.00

126.93

A

C

ATOM

2186

CB

ARG

A

278

−1.410

−78.951

6.574

1.00

127.33

A

C

ATOM

2187

CG

ARG

A

278

−0.092

−78.803

7.350

1.00

129.03

A

C

ATOM

2188

CD

ARG

A

278

0.240

−79.993

8.237

1.00

130.93

A

C

ATOM

2189

NE

ARG

A

278

1.357

−79.662

9.124

1.00

132.79

A

N

ATOM

2190

CZ

ARG

A

278

1.716

−80.363

10.200

1.00

133.78

A

C

ATOM

2191

NH1

ARG

A

278

1.048

−81.460

10.548

1.00

134.11

A

N

ATOM

2192

NH2

ARG

A

278

2.749

−79.962

10.934

1.00

133.73

A

N

ATOM

2193

C

ARG

A

278

−0.568

−77.386

4.785

1.00

126.83

A

C

ATOM

2194

O

ARG

A

278

−0.299

−78.103

3.819

1.00

127.02

A

O

ATOM

2195

N

ILE

A

279

0.115

−76.288

5.085

1.00

126.77

A

N

ATOM

2196

CA

ILE

A

279

1.178

−75.768

4.224

1.00

126.81

A

C

ATOM

2197

CB

ILE

A

279

1.410

−74.248

4.474

1.00

126.66

A

C

ATOM

2198

CG1

ILE

A

279

2.498

−73.694

3.555

1.00

126.38

A

C

ATOM

2199

CD1

ILE

A

279

2.496

−72.187

3.461

1.00

126.72

A

C

ATOM

2200

CG2

ILE

A

279

1.688

−73.960

5.957

1.00

126.34

A

C

ATOM

2201

C

ILE

A

279

2.463

−76.573

4.400

1.00

127.10

A

C

ATOM

2202

O

ILE

A

279

2.790

−76.980

5.518

1.00

127.34

A

O

ATOM

2203

N

ASN

A

280

3.167

−76.826

3.293

1.00

127.21

A

N

ATOM

2204

CA

ASN

A

280

4.412

−77.608

3.310

1.00

127.25

A

C

ATOM

2205

CB

ASN

A

280

4.213

−78.984

3.986

1.00

127.47

A

C

ATOM

2206

CG

ASN

A

280

2.819

−79.580

3.740

1.00

128.10

A

C

ATOM

2207

OD1

ASN

A

280

2.404

−79.779

2.597

1.00

129.09

A

O

ATOM

2208

ND2

ASN

A

280

2.096

−79.861

4.823

1.00

128.28

A

N

ATOM

2209

C

ASN

A

280

5.072

−77.797

1.947

1.00

127.06

A

C

ATOM

2210

O

ASN

A

280

4.403

−78.102

0.957

1.00

126.98

A

O

ATOM

2211

N

SER

A

281

6.394

−77.615

1.925

1.00

126.94

A

N

ATOM

2212

CA

SER

A

281

7.261

−77.989

0.795

1.00

126.75

A

C

ATOM

2213

CB

SER

A

281

7.322

−79.522

0.629

1.00

126.86

A

C

ATOM

2214

OG

SER

A

281

7.696

−80.182

1.832

1.00

127.14

A

O

ATOM

2215

C

SER

A

281

6.903

−77.312

−0.538

1.00

126.49

A

C

ATOM

2216

O

SER

A

281

7.233

−76.144

−0.751

1.00

126.39

A

O

ATOM

2217

N

ARG

A

282

6.220

−78.059

−1.412

1.00

126.17

A

N

ATOM

2218

CA

ARG

A

282

5.963

−77.654

−2.803

1.00

125.69

A

C

ATOM

2219

CB

ARG

A

282

6.149

−78.848

−3.762

1.00

125.91

A

C

ATOM

2220

CG

ARG

A

282

7.526

−79.538

−3.699

1.00

126.51

A

C

ATOM

2221

CD

ARG

A

282

8.123

−79.751

−5.103

1.00

127.19

A

C

ATOM

2222

NE

ARG

A

282

7.630

−80.955

−5.778

1.00

126.98

A

N

ATOM

2223

CZ

ARG

A

282

8.405

−81.938

−6.237

1.00

126.97

A

C

ATOM

2224

NH1

ARG

A

282

9.728

−81.879

−6.109

1.00

126.64

A

N

ATOM

2225

NH2

ARG

A

282

7.853

−82.984

−6.835

1.00

126.83

A

N

ATOM

2226

C

ARG

A

282

4.583

−77.015

−3.024

1.00

125.16

A

C

ATOM

2227

O

ARG

A

282

4.027

−77.084

−4.130

1.00

125.20

A

O

ATOM

2228

N

ASN

A

283

4.044

−76.387

−1.978

1.00

124.36

A

N

ATOM

2229

CA

ASN

A

283

2.733

−75.736

−2.058

1.00

123.38

A

C

ATOM

2230

CB

ASN

A

283

1.650

−76.572

−1.343

1.00

123.52

A

C

ATOM

2231

CG

ASN

A

283

1.763

−76.531

0.192

1.00

123.93

A

C

ATOM

2232

OD1

ASN

A

283

2.633

−75.861

0.765

1.00

124.69

A

O

ATOM

2233

ND2

ASN

A

283

0.872

−77.254

0.857

1.00

123.45

A

N

ATOM

2234

C

ASN

A

283

2.724

−74.293

−1.556

1.00

122.54

A

C

ATOM

2235

O

ASN

A

283

1.655

−73.712

−1.361

1.00

122.71

A

O

ATOM

2236

N

LEU

A

284

3.905

−73.714

−1.345

1.00

121.30

A

N

ATOM

2237

CA

LEU

A

284

3.991

−72.316

−0.902

1.00

120.23

A

C

ATOM

2238

CB

LEU

A

284

5.308

−72.019

−0.174

1.00

120.38

A

C

ATOM

2239

CG

LEU

A

284

6.219

−73.117

0.389

1.00

120.53

A

C

ATOM

2240

CD1

LEU

A

284

7.386

−72.454

1.097

1.00

120.04

A

C

ATOM

2241

CD2

LEU

A

284

5.499

−74.116

1.313

1.00

121.01

A

C

ATOM

2242

C

LEU

A

284

3.811

−71.379

−2.094

1.00

119.34

A

C

ATOM

2243

O

LEU

A

284

3.693

−70.162

−1.941

1.00

119.18

A

O

ATOM

2244

N

SER

A

285

3.811

−71.976

−3.282

1.00

118.34

A

N

ATOM

2245

CA

SER

A

285

3.418

−71.322

−4.525

1.00

117.26

A

C

ATOM

2246

CB

SER

A

285

3.626

−72.296

−5.683

1.00

117.36

A

C

ATOM

2247

OG

SER

A

285

3.130

−73.598

−5.374

1.00

116.48

A

O

ATOM

2248

C

SER

A

285

1.949

−70.898

−4.511

1.00

116.61

A

C

ATOM

2249

O

SER

A

285

1.598

−69.850

−5.069

1.00

116.53

A

O

ATOM

2250

N

ASP

A

286

1.119

−71.719

−3.856

1.00

115.46

A

N

ATOM

2251

CA

ASP

A

286

−0.343

−71.666

−3.923

1.00

114.40

A

C

ATOM

2252

CB

ASP

A

286

−0.931

−72.901

−3.253

1.00

114.37

A

C

ATOM

2253

CG

ASP

A

286

−0.467

−74.181

−3.891

1.00

114.39

A

C

ATOM

2254

OD1

ASP

A

286

0.662

−74.214

−4.419

1.00

115.99

A

O

ATOM

2255

OD2

ASP

A

286

−1.226

−75.162

−3.863

1.00

113.96

A

O

ATOM

2256

C

ASP

A

286

−0.973

−70.447

−3.292

1.00

113.73

A

C

ATOM

2257

O

ASP

A

286

−0.418

−69.860

−2.374

1.00

113.64

A

O

ATOM

2258

N

ILE

A

287

−2.153

−70.091

−3.788

1.00

113.03

A

N

ATOM

2259

CA

ILE

A

287

−2.944

−68.989

−3.241

1.00

112.50

A

C

ATOM

2260

CB

ILE

A

287

−4.243

−68.727

−4.095

1.00

112.53

A

C

ATOM

2261

CG1

ILE

A

287

−5.004

−67.491

−3.614

1.00

112.14

A

C

ATOM

2262

CD1

ILE

A

287

−4.324

−66.201

−3.902

1.00

112.17

A

C

ATOM

2263

CG2

ILE

A

287

−5.183

−69.940

−4.097

1.00

112.69

A

C

ATOM

2264

C

ILE

A

287

−3.284

−69.213

−1.763

1.00

112.05

A

C

ATOM

2265

O

ILE

A

287

−3.176

−68.298

−0.944

1.00

111.77

A

O

ATOM

2266

N

GLY

A

288

−3.655

−70.446

−1.433

1.00

111.65

A

N

ATOM

2267

CA

GLY

A

288

−4.117

−70.791

−0.097

1.00

111.42

A

C

ATOM

2268

C

GLY

A

288

−3.144

−70.596

1.049

1.00

111.18

A

C

ATOM

2269

O

GLY

A

288

−3.483

−70.836

2.199

1.00

111.17

A

O

ATOM

2270

N

THR

A

289

−1.932

−70.163

0.745

1.00

111.16

A

N

ATOM

2271

CA

THR

A

289

−0.940

−69.935

1.781

1.00

111.06

A

C

ATOM

2272

CB

THR

A

289

0.478

−69.814

1.191

1.00

110.93

A

C

ATOM

2273

OG1

THR

A

289

0.571

−68.624

0.403

1.00

110.66

A

O

ATOM

2274

CG2

THR

A

289

0.788

−71.013

0.318

1.00

110.68

A

C

ATOM

2275

C

THR

A

289

−1.289

−68.676

2.568

1.00

111.19

A

C

ATOM

2276

O

THR

A

289

−0.880

−68.523

3.721

1.00

111.04

A

O

ATOM

2277

N

ILE

A

290

−2.060

−67.789

1.939

1.00

111.39

A

N

ATOM

2278

CA

ILE

A

290

−2.389

−66.487

2.528

1.00

111.58

A

C

ATOM

2279

CB

ILE

A

290

−1.880

−65.310

1.654

1.00

111.58

A

C

ATOM

2280

CG1

ILE

A

290

−2.455

−65.389

0.233

1.00

111.41

A

C

ATOM

2281

CD1

ILE

A

290

−2.664

−64.031

−0.417

1.00

111.16

A

C

ATOM

2282

CG2

ILE

A

290

−0.356

−65.289

1.622

1.00

112.15

A

C

ATOM

2283

C

ILE

A

290

−3.874

−66.275

2.806

1.00

111.55

A

C

ATOM

2284

O

ILE

A

290

−4.367

−65.160

2.674

1.00

111.58

A

O

ATOM

2285

N

MET

A

291

−4.584

−67.329

3.194

1.00

111.76

A

N

ATOM

2286

CA

MET

A

291

−6.002

−67.192

3.490

1.00

112.15

A

C

ATOM

2287

CB

MET

A

291

−6.803

−66.950

2.213

1.00

112.16

A

C

ATOM

2288

CG

MET

A

291

−6.823

−68.099

1.224

1.00

111.43

A

C

ATOM

2289

SD

MET

A

291

−8.046

−67.796

−0.062

1.00

110.98

A

S

ATOM

2290

CE

MET

A

291

−7.503

−66.241

−0.775

1.00

108.38

A

C

ATOM

2291

C

MET

A

291

−6.630

−68.340

4.259

1.00

112.75

A

C

ATOM

2292

O

MET

A

291

−6.300

−69.501

4.039

1.00

112.78

A

O

ATOM

2293

N

ARG

A

292

−7.540

−67.983

5.162

1.00

113.41

A

N

ATOM

2294

CA

ARG

A

292

−8.398

−68.933

5.842

1.00

114.12

A

C

ATOM

2295

CB

ARG

A

292

−8.993

−68.291

7.084

1.00

114.22

A

C

ATOM

2296

CG

ARG

A

292

−8.460

−68.779

8.407

1.00

114.69

A

C

ATOM

2297

CD

ARG

A

292

−9.207

−68.065

9.530

1.00

115.78

A

C

ATOM

2298

NE

ARG

A

292

−9.079

−66.610

9.408

1.00

116.24

A

N

ATOM

2299

CZ

ARG

A

292

−9.924

−65.722

9.925

1.00

116.72

A

C

ATOM

2300

NH1

ARG

A

292

−10.994

−66.115

10.609

1.00

117.49

A

N

ATOM

2301

NH2

ARG

A

292

−9.703

−64.428

9.747

1.00

116.79

A

N

ATOM

2302

C

ARG

A

292

−9.531

−69.249

4.900

1.00

114.61

A

C

ATOM

2303

O

ARG

A

292

−10.054

−68.347

4.255

1.00

114.90

A

O

ATOM

2304

N

VAL

A

293

−9.916

−70.518

4.818

1.00

115.18

A

N

ATOM

2305

CA

VAL

A

293

−11.056

−70.918

3.999

1.00

115.88

A

C

ATOM

2306

CB

VAL

A

293

−10.631

−71.731

2.756

1.00

115.75

A

C

ATOM

2307

CG1

VAL

A

293

−11.817

−71.978

1.832

1.00

115.27

A

C

ATOM

2308

CG2

VAL

A

293

−9.531

−71.009

2.005

1.00

116.00

A

C

ATOM

2309

C

VAL

A

293

−12.012

−71.731

4.856

1.00

116.64

A

C

ATOM

2310

O

VAL

A

293

−11.636

−72.751

5.425

1.00

116.87

A

O

ATOM

2311

N

VAL

A

294

−13.249

−71.263

4.951

1.00

117.53

A

N

ATOM

2312

CA

VAL

A

294

−14.262

−71.906

5.779

1.00

118.26

A

C

ATOM

2313

CB

VAL

A

294

−14.502

−71.091

7.103

1.00

118.22

A

C

ATOM

2314

CG1

VAL

A

294

−13.912

−69.678

7.016

1.00

118.10

A

C

ATOM

2315

CG2

VAL

A

294

−15.967

−71.042

7.500

1.00

118.33

A

C

ATOM

2316

C

VAL

A

294

−15.537

−72.146

4.959

1.00

118.92

A

C

ATOM

2317

O

VAL

A

294

−15.997

−71.245

4.256

1.00

119.08

A

O

ATOM

2318

N

GLU

A

295

−16.071

−73.371

5.019

1.00

119.80

A

N

ATOM

2319

CA

GLU

A

295

−17.357

−73.716

4.398

1.00

120.84

A

C

ATOM

2320

CB

GLU

A

295

−17.745

−75.188

4.625

1.00

120.76

A

C

ATOM

2321

CG

GLU

A

295

−16.667

−76.247

4.427

1.00

120.38

A

C

ATOM

2322

CD

GLU

A

295

−16.858

−77.469

5.325

1.00

118.91

A

C

ATOM

2323

OE1

GLU

A

295

−16.632

−77.357

6.550

1.00

117.49

A

O

ATOM

2324

OE2

GLU

A

295

−17.218

−78.545

4.800

1.00

119.03

A

O

ATOM

2325

C

GLU

A

295

−18.441

−72.878

5.056

1.00

121.92

A

C

ATOM

2326

O

GLU

A

295

−18.289

−72.443

6.202

1.00

122.06

A

O

ATOM

2327

N

LEU

A

296

−19.543

−72.666

4.345

1.00

123.02

A

N

ATOM

2328

CA

LEU

A

296

−20.689

−71.985

4.922

1.00

123.95

A

C

ATOM

2329

CB

LEU

A

296

−20.870

−70.584

4.334

1.00

123.92

A

C

ATOM

2330

CG

LEU

A

296

−19.812

−69.540

4.724

1.00

124.04

A

C

ATOM

2331

CD1

LEU

A

296

−20.104

−68.189

4.102

1.00

123.49

A

C

ATOM

2332

CD2

LEU

A

296

−19.698

−69.399

6.238

1.00

125.01

A

C

ATOM

2333

C

LEU

A

296

−21.930

−72.821

4.740

1.00

124.81

A

C

ATOM

2334

O

LEU

A

296

−22.099

−73.495

3.717

1.00

124.82

A

O

ATOM

2335

N

SER

A

297

−22.779

−72.782

5.761

1.00

126.02

A

N

ATOM

2336

CA

SER

A

297

−24.003

−73.572

5.807

1.00

127.25

A

C

ATOM

2337

CB

SER

A

297

−24.463

−73.724

7.253

1.00

127.13

A

C

ATOM

2338

OG

SER

A

297

−23.407

−74.194

8.074

1.00

127.28

A

O

ATOM

2339

C

SER

A

297

−25.092

−72.906

4.968

1.00

128.15

A

C

ATOM

2340

O

SER

A

297

−25.291

−71.691

5.066

1.00

128.32

A

O

ATOM

2341

N

PRO

A

298

−25.800

−73.694

4.139

1.00

128.94

A

N

ATOM

2342

CA

PRO

A

298

−26.773

−73.100

3.211

1.00

129.74

A

C

ATOM

2343

CB

PRO

A

298

−26.762

−74.084

2.037

1.00

129.72

A

C

ATOM

2344

CG

PRO

A

298

−26.352

−75.416

2.652

1.00

129.26

A

C

ATOM

2345

CD

PRO

A

298

−25.701

−75.158

3.986

1.00

128.74

A

C

ATOM

2346

C

PRO

A

298

−28.199

−72.939

3.779

1.00

130.60

A

C

ATOM

2347

O

PRO

A

298

−28.521

−73.506

4.833

1.00

130.62

A

O

ATOM

2348

N

LEU

A

299

−29.037

−72.159

3.088

1.00

131.59

A

N

ATOM

2349

CA

LEU

A

299

−30.481

−72.139

3.370

1.00

132.52

A

C

ATOM

2350

CB

LEU

A

299

−31.151

−70.850

2.863

1.00

132.21

A

C

ATOM

2351

CG

LEU

A

299

−31.246

−69.571

3.716

1.00

132.15

A

C

ATOM

2352

CD1

LEU

A

299

−31.642

−69.840

5.167

1.00

131.79

A

C

ATOM

2353

CD2

LEU

A

299

−29.961

−68.760

3.667

1.00

132.58

A

C

ATOM

2354

C

LEU

A

299

−31.146

−73.367

2.746

1.00

133.36

A

C

ATOM

2355

O

LEU

A

299

−30.573

−74.463

2.746

1.00

133.49

A

O

ATOM

2356

N

LYS

A

300

−32.357

−73.188

2.226

1.00

134.44

A

N

ATOM

2357

CA

LYS

A

300

−33.057

−74.260

1.516

1.00

135.47

A

C

ATOM

2358

CB

LYS

A

300

−34.149

−74.888

2.399

1.00

135.37

A

C

ATOM

2359

CG

LYS

A

300

−34.020

−74.645

3.907

1.00

135.09

A

C

ATOM

2360

CD

LYS

A

300

−33.073

−75.607

4.589

1.00

134.40

A

C

ATOM

2361

CE

LYS

A

300

−32.671

−75.038

5.928

1.00

134.47

A

C

ATOM

2362

NZ

LYS

A

300

−31.198

−75.066

6.110

1.00

134.51

A

N

ATOM

2363

C

LYS

A

300

−33.654

−73.737

0.197

1.00

136.28

A

C

ATOM

2364

O

LYS

A

300

−34.594

−74.322

−0.350

1.00

136.32

A

O

ATOM

2365

N

GLY

A

301

−33.098

−72.631

−0.302

1.00

137.14

A

N

ATOM

2366

CA

GLY

A

301

−33.564

−72.006

−1.538

1.00

138.22

A

C

ATOM

2367

C

GLY

A

301

−32.778

−72.425

−2.773

1.00

139.08

A

C

ATOM

2368

O

GLY

A

301

−33.117

−72.035

−3.898

1.00

139.24

A

O

ATOM

2369

N

SER

A

302

−31.727

−73.221

−2.568

1.00

139.63

A

N

ATOM

2370

CA

SER

A

302

−30.875

−73.683

−3.664

1.00

140.06

A

C

ATOM

2371

CB

SER

A

302

−29.608

−74.353

−3.116

1.00

140.19

A

C

ATOM

2372

OG

SER

A

302

−28.788

−73.422

−2.421

1.00

140.01

A

O

ATOM

2373

C

SER

A

302

−31.633

−74.621

−4.610

1.00

140.31

A

C

ATOM

2374

O

SER

A

302

−31.893

−75.781

−4.276

1.00

140.17

A

O

ATOM

2375

N

VAL

A

303

−31.975

−74.092

−5.787

1.00

140.76

A

N

ATOM

2376

CA

VAL

A

303

−32.798

−74.790

−6.794

1.00

141.09

A

C

ATOM

2377

CB

VAL

A

303

−33.786

−73.786

−7.504

1.00

141.05

A

C

ATOM

2378

CG1

VAL

A

303

−33.040

−72.857

−8.450

1.00

141.07

A

C

ATOM

2379

CG2

VAL

A

303

−34.944

−74.512

−8.214

1.00

140.76

A

C

ATOM

2380

C

VAL

A

303

−31.957

−75.614

−7.806

1.00

141.33

A

C

ATOM

2381

O

VAL

A

303

−32.494

−76.187

−8.763

1.00

141.46

A

O

ATOM

2382

N

SER

A

304

−30.642

−75.669

−7.576

1.00

141.52

A

N

ATOM

2383

CA

SER

A

304

−29.724

−76.537

−8.340

1.00

141.55

A

C

ATOM

2384

CB

SER

A

304

−28.263

−76.277

−7.933

1.00

141.59

A

C

ATOM

2385

OG

SER

A

304

−28.160

−75.759

−6.613

1.00

141.11

A

O

ATOM

2386

C

SER

A

304

−30.085

−78.033

−8.218

1.00

141.57

A

C

ATOM

2387

O

SER

A

304

−30.584

−78.471

−7.176

1.00

141.59

A

O

ATOM

2388

N

TRP

A

305

−29.830

−78.796

−9.288

1.00

141.53

A

N

ATOM

2389

CA

TRP

A

305

−30.328

−80.189

−9.465

1.00

141.37

A

C

ATOM

2390

CB

TRP

A

305

−29.330

−81.232

−8.952

1.00

141.57

A

C

ATOM

2391

CG

TRP

A

305

−27.936

−81.029

−9.404

1.00

142.85

A

C

ATOM

2392

CD1

TRP

A

305

−27.382

−81.474

−10.566

1.00

143.75

A

C

ATOM

2393

NE1

TRP

A

305

−26.057

−81.104

−10.631

1.00

144.75

A

N

ATOM

2394

CE2

TRP

A

305

−25.733

−80.404

−9.498

1.00

145.21

A

C

ATOM

2395

CD2

TRP

A

305

−26.897

−80.341

−8.695

1.00

144.52

A

C

ATOM

2396

CE3

TRP

A

305

−26.835

−79.673

−7.462

1.00

144.74

A

C

ATOM

2397

CZ3

TRP

A

305

−25.627

−79.096

−7.074

1.00

145.23

A

C

ATOM

2398

CH2

TRP

A

305

−24.483

−79.171

−7.896

1.00

145.43

A

C

ATOM

2399

CZ2

TRP

A

305

−24.515

−79.820

−9.107

1.00

145.64

A

C

ATOM

2400

C

TRP

A

305

−31.716

−80.445

−8.853

1.00

140.79

A

C

ATOM

2401

O

TRP

A

305

−31.997

−81.543

−8.351

1.00

140.57

A

O

ATOM

2402

N

THR

A

306

−32.567

−79.417

−8.915

1.00

140.15

A

N

ATOM

2403

CA

THR

A

306

−33.928

−79.422

−8.353

1.00

139.43

A

C

ATOM

2404

CB

THR

A

306

−34.857

−80.505

−9.029

1.00

139.57

A

C

ATOM

2405

OG1

THR

A

306

−34.249

−81.804

−8.961

1.00

138.88

A

O

ATOM

2406

CG2

THR

A

306

−35.123

−80.144

−10.493

1.00

139.19

A

C

ATOM

2407

C

THR

A

306

−33.975

−79.433

−6.798

1.00

138.86

A

C

ATOM

2408

O

THR

A

306

−34.821

−80.098

−6.175

1.00

138.75

A

O

ATOM

2409

N

GLY

A

307

−33.072

−78.669

−6.183

1.00

137.97

A

N

ATOM

2410

CA

GLY

A

307

−33.010

−78.564

−4.721

1.00

136.97

A

C

ATOM

2411

C

GLY

A

307

−31.772

−79.152

−4.051

1.00

136.09

A

C

ATOM

2412

O

GLY

A

307

−31.526

−78.884

−2.874

1.00

136.13

A

O

ATOM

2413

N

LYS

A

308

−31.003

−79.941

−4.809

1.00

134.96

A

N

ATOM

2414

CA

LYS

A

308

−29.826

−80.692

−4.334

1.00

133.92

A

C

ATOM

2415

CB

LYS

A

308

−29.079

−81.293

−5.534

1.00

133.96

A

C

ATOM

2416

CG

LYS

A

308

−29.038

−82.818

−5.596

1.00

134.24

A

C

ATOM

2417

CD

LYS

A

308

−30.411

−83.448

−5.790

1.00

133.99

A

C

ATOM

2418

CE

LYS

A

308

−30.337

−84.953

−5.587

1.00

133.51

A

C

ATOM

2419

NZ

LYS

A

308

−31.660

−85.592

−5.805

1.00

133.21

A

N

ATOM

2420

C

LYS

A

308

−28.806

−79.962

−3.432

1.00

133.13

A

C

ATOM

2421

O

LYS

A

308

−28.616

−78.742

−3.552

1.00

133.33

A

O

ATOM

2422

N

PRO

A

309

−28.151

−80.720

−2.522

1.00

132.02

A

N

ATOM

2423

CA

PRO

A

309

−27.011

−80.289

−1.698

1.00

130.88

A

C

ATOM

2424

CB

PRO

A

309

−26.411

−81.628

−1.208

1.00

131.12

A

C

ATOM

2425

CG

PRO

A

309

−27.354

−82.744

−1.745

1.00

131.67

A

C

ATOM

2426

CD

PRO

A

309

−28.630

−82.045

−2.083

1.00

131.91

A

C

ATOM

2427

C

PRO

A

309

−25.920

−79.470

−2.411

1.00

129.52

A

C

ATOM

2428

O

PRO

A

309

−25.245

−79.976

−3.320

1.00

129.59

A

O

ATOM

2429

N

VAL

A

310

−25.772

−78.211

−1.992

1.00

127.65

A

N

ATOM

2430

CA

VAL

A

310

−24.582

−77.389

−2.285

1.00

125.53

A

C

ATOM

2431

CB

VAL

A

310

−24.842

−76.267

−3.336

1.00

125.64

A

C

ATOM

2432

CG1

VAL

A

310

−24.954

−76.843

−4.731

1.00

125.70

A

C

ATOM

2433

CG2

VAL

A

310

−26.070

−75.436

−2.978

1.00

125.70

A

C

ATOM

2434

C

VAL

A

310

−24.062

−76.758

−0.990

1.00

123.84

A

C

ATOM

2435

O

VAL

A

310

−24.697

−76.884

0.058

1.00

123.86

A

O

ATOM

2436

N

SER

A

311

−22.910

−76.092

−1.066

1.00

121.54

A

N

ATOM

2437

CA

SER

A

311

−22.316

−75.390

0.076

1.00

119.36

A

C

ATOM

2438

CB

SER

A

311

−21.397

−76.326

0.863

1.00

119.51

A

C

ATOM

2439

OG

SER

A

311

−22.089

−77.486

1.292

1.00

119.01

A

O

ATOM

2440

C

SER

A

311

−21.535

−74.174

−0.420

1.00

117.87

A

C

ATOM

2441

O

SER

A

311

−21.243

−74.076

−1.615

1.00

117.96

A

O

ATOM

2442

N

TYR

A

312

−21.198

−73.250

0.479

1.00

115.69

A

N

ATOM

2443

CA

TYR

A

312

−20.486

−72.029

0.075

1.00

113.79

A

C

ATOM

2444

CB

TYR

A

312

−21.440

−70.830

0.034

1.00

113.95

A

C

ATOM

2445

CG

TYR

A

312

−22.589

−71.079

−0.915

1.00

114.45

A

C

ATOM

2446

CD1

TYR

A

312

−22.454

−70.835

−2.277

1.00

114.96

A

C

ATOM

2447

CE1

TYR

A

312

−23.496

−71.086

−3.158

1.00

114.97

A

C

ATOM

2448

CZ

TYR

A

312

−24.681

−71.597

−2.682

1.00

115.11

A

C

ATOM

2449

OH

TYR

A

312

−25.703

−71.837

−3.560

1.00

116.33

A

O

ATOM

2450

CE2

TYR

A

312

−24.846

−71.863

−1.335

1.00

115.35

A

C

ATOM

2451

CD2

TYR

A

312

−23.799

−71.609

−0.459

1.00

115.34

A

C

ATOM

2452

C

TYR

A

312

−19.230

−71.776

0.907

1.00

112.26

A

C

ATOM

2453

O

TYR

A

312

−18.986

−72.492

1.870

1.00

112.27

A

O

ATOM

2454

N

TYR

A

313

−18.427

−70.783

0.519

1.00

110.19

A

N

ATOM

2455

CA

TYR

A

313

−17.052

−70.674

1.004

1.00

108.18

A

C

ATOM

2456

CB

TYR

A

313

−16.108

−71.326

−0.001

1.00

107.76

A

C

ATOM

2457

CG

TYR

A

313

−16.416

−72.778

−0.256

1.00

106.26

A

C

ATOM

2458

CD1

TYR

A

313

−15.920

−73.766

0.580

1.00

105.49

A

C

ATOM

2459

CE1

TYR

A

313

−16.199

−75.098

0.352

1.00

105.51

A

C

ATOM

2460

CZ

TYR

A

313

−16.994

−75.456

−0.720

1.00

105.15

A

C

ATOM

2461

OH

TYR

A

313

−17.279

−76.781

−0.941

1.00

105.20

A

O

ATOM

2462

CE2

TYR

A

313

−17.500

−74.494

−1.564

1.00

104.97

A

C

ATOM

2463

CD2

TYR

A

313

−17.209

−73.162

−1.328

1.00

105.35

A

C

ATOM

2464

C

TYR

A

313

−16.584

−69.258

1.289

1.00

107.55

A

C

ATOM

2465

O

TYR

A

313

−16.663

−68.384

0.437

1.00

107.42

A

O

ATOM

2466

N

LEU

A

314

−16.068

−69.037

2.489

1.00

106.83

A

N

ATOM

2467

CA

LEU

A

314

−15.602

−67.710

2.863

1.00

106.32

A

C

ATOM

2468

CB

LEU

A

314

−16.351

−67.204

4.105

1.00

106.10

A

C

ATOM

2469

CG

LEU

A

314

−15.674

−66.194

5.037

1.00

105.66

A

C

ATOM

2470

CD1

LEU

A

314

−15.310

−64.912

4.332

1.00

105.20

A

C

ATOM

2471

CD2

LEU

A

314

−16.559

−65.908

6.223

1.00

105.51

A

C

ATOM

2472

C

LEU

A

314

−14.078

−67.654

3.036

1.00

106.10

A

C

ATOM

2473

O

LEU

A

314

−13.517

−68.217

3.975

1.00

106.33

A

O

ATOM

2474

N

HIS

A

315

−13.418

−66.976

2.108

1.00

105.77

A

N

ATOM

2475

CA

HIS

A

315

−11.980

−66.846

2.141

1.00

105.38

A

C

ATOM

2476

CB

HIS

A

315

−11.390

−66.844

0.734

1.00

104.88

A

C

ATOM

2477

CG

HIS

A

315

−11.887

−67.943

−0.153

1.00

103.08

A

C

ATOM

2478

ND1

HIS

A

315

−12.941

−67.778

−1.022

1.00

101.22

A

N

ATOM

2479

CE1

HIS

A

315

−13.142

−68.901

−1.687

1.00

100.76

A

C

ATOM

2480

NE2

HIS

A

315

−12.249

−69.786

−1.287

1.00

100.83

A

N

ATOM

2481

CD2

HIS

A

315

−11.447

−69.209

−0.335

1.00

101.73

A

C

ATOM

2482

C

HIS

A

315

−11.650

−65.529

2.801

1.00

106.02

A

C

ATOM

2483

O

HIS

A

315

−11.980

−64.471

2.266

1.00

106.12

A

O

ATOM

2484

N

THR

A

316

−11.013

−65.590

3.968

1.00

106.77

A

N

ATOM

2485

CA

THR

A

316

−10.501

−64.387

4.628

1.00

107.28

A

C

ATOM

2486

CB

THR

A

316

−10.833

−64.352

6.142

1.00

107.10

A

C

ATOM

2487

OG1

THR

A

316

−11.948

−65.207

6.427

1.00

107.47

A

O

ATOM

2488

CG2

THR

A

316

−11.152

−62.941

6.591

1.00

106.54

A

C

ATOM

2489

C

THR

A

316

−8.995

−64.391

4.444

1.00

107.83

A

C

ATOM

2490

O

THR

A

316

−8.346

−65.394

4.738

1.00

107.85

A

O

ATOM

2491

N

ILE

A

317

−8.450

−63.286

3.935

1.00

108.68

A

N

ATOM

2492

CA

ILE

A

317

−7.002

−63.138

3.728

1.00

109.53

A

C

ATOM

2493

CB

ILE

A

317

−6.646

−61.827

2.930

1.00

109.36

A

C

ATOM

2494

CG1

ILE

A

317

−7.082

−61.913

1.460

1.00

108.76

A

C

ATOM

2495

CD1

ILE

A

317

−6.416

−62.990

0.648

1.00

107.83

A

C

ATOM

2496

CG2

ILE

A

317

−5.165

−61.473

3.039

1.00

109.13

A

C

ATOM

2497

C

ILE

A

317

−6.282

−63.138

5.073

1.00

110.50

A

C

ATOM

2498

O

ILE

A

317

−6.424

−62.205

5.863

1.00

110.77

A

O

ATOM

2499

N

ASP

A

318

−5.537

−64.204

5.342

1.00

111.78

A

N

ATOM

2500

CA

ASP

A

318

−4.662

−64.238

6.507

1.00

113.00

A

C

ATOM

2501

CB

ASP

A

318

−5.169

−65.224

7.569

1.00

113.04

A

C

ATOM

2502

CG

ASP

A

318

−4.698

−64.862

8.990

1.00

113.30

A

C

ATOM

2503

OD1

ASP

A

318

−4.359

−63.679

9.249

1.00

112.20

A

O

ATOM

2504

OD2

ASP

A

318

−4.677

−65.771

9.851

1.00

113.57

A

O

ATOM

2505

C

ASP

A

318

−3.218

−64.537

6.102

1.00

113.74

A

C

ATOM

2506

O

ASP

A

318

−2.819

−65.698

5.955

1.00

113.50

A

O

ATOM

2507

N

ARG

A

319

−2.448

−63.466

5.916

1.00

114.82

A

N

ATOM

2508

CA

ARG

A

319

−1.025

−63.569

5.592

1.00

116.06

A

C

ATOM

2509

CB

ARG

A

319

−0.505

−62.242

5.024

1.00

116.22

A

C

ATOM

2510

CG

ARG

A

319

−0.350

−62.278

3.513

1.00

116.72

A

C

ATOM

2511

CD

ARG

A

319

−0.663

−60.954

2.854

1.00

117.45

A

C

ATOM

2512

NE

ARG

A

319

−1.286

−61.187

1.553

1.00

118.04

A

N

ATOM

2513

CZ

ARG

A

319

−1.598

−60.244

0.670

1.00

118.36

A

C

ATOM

2514

NH1

ARG

A

319

−1.348

−58.964

0.915

1.00

118.65

A

N

ATOM

2515

NH2

ARG

A

319

−2.172

−60.588

−0.470

1.00

118.99

A

N

ATOM

2516

C

ARG

A

319

−0.180

−64.033

6.782

1.00

116.65

A

C

ATOM

2517

O

ARG

A

319

1.042

−63.842

6.803

1.00

116.54

A

O

ATOM

2518

N

THR

A

320

−0.854

−64.655

7.753

1.00

117.47

A

N

ATOM

2519

CA

THR

A

320

−0.242

−65.146

8.985

1.00

117.98

A

C

ATOM

2520

CB

THR

A

320

−1.145

−64.875

10.202

1.00

117.87

A

C

ATOM

2521

OG1

THR

A

320

−0.943

−63.524

10.626

1.00

117.55

A

O

ATOM

2522

CG2

THR

A

320

−0.832

−65.816

11.364

1.00

117.83

A

C

ATOM

2523

C

THR

A

320

0.111

−66.617

8.874

1.00

118.52

A

C

ATOM

2524

O

THR

A

320

1.154

−67.028

9.369

1.00

118.75

A

O

ATOM

2525

N

ILE

A

321

−0.744

−67.396

8.209

1.00

119.23

A

N

ATOM

2526

CA

ILE

A

321

−0.449

−68.803

7.907

1.00

120.07

A

C

ATOM

2527

CB

ILE

A

321

−1.437

−69.445

6.878

1.00

120.16

A

C

ATOM

2528

CG1

ILE

A

321

−2.720

−68.616

6.664

1.00

120.48

A

C

ATOM

2529

CD1

ILE

A

321

−3.766

−68.700

7.770

1.00

121.91

A

C

ATOM

2530

CG2

ILE

A

321

−1.693

−70.910

7.222

1.00

120.46

A

C

ATOM

2531

C

ILE

A

321

0.947

−68.920

7.302

1.00

120.58

A

C

ATOM

2532

O

ILE

A

321

1.645

−69.915

7.508

1.00

120.51

A

O

ATOM

2533

N

LEU

A

322

1.331

−67.894

6.541

1.00

121.34

A

N

ATOM

2534

CA

LEU

A

322

2.644

−67.826

5.928

1.00

121.99

A

C

ATOM

2535

CB

LEU

A

322

2.710

−66.707

4.879

1.00

121.91

A

C

ATOM

2536

CG

LEU

A

322

3.762

−66.808

3.759

1.00

122.11

A

C

ATOM

2537

CD1

LEU

A

322

3.486

−67.954

2.783

1.00

121.91

A

C

ATOM

2538

CD2

LEU

A

322

3.862

−65.496

2.996

1.00

122.27

A

C

ATOM

2539

C

LEU

A

322

3.681

−67.631

7.019

1.00

122.48

A

C

ATOM

2540

O

LEU

A

322

4.559

−68.479

7.183

1.00

122.74

A

O

ATOM

2541

N

GLU

A

323

3.553

−66.539

7.779

1.00

123.00

A

N

ATOM

2542

CA

GLU

A

323

4.439

−66.246

8.911

1.00

123.57

A

C

ATOM

2543

CB

GLU

A

323

3.881

−65.101

9.755

1.00

123.45

A

C

ATOM

2544

CG

GLU

A

323

3.922

−63.730

9.105

1.00

123.81

A

C

ATOM

2545

CD

GLU

A

323

2.964

−62.733

9.764

1.00

124.47

A

C

ATOM

2546

OE1

GLU

A

323

2.298

−63.110

10.755

1.00

124.88

A

O

ATOM

2547

OE2

GLU

A

323

2.872

−61.575

9.287

1.00

124.20

A

O

ATOM

2548

C

GLU

A

323

4.649

−67.471

9.805

1.00

124.12

A

C

ATOM

2549

O

GLU

A

323

5.779

−67.772

10.197

1.00

124.30

A

O

ATOM

2550

N

ASN

A

324

3.565

−68.179

10.116

1.00

124.70

A

N

ATOM

2551

CA

ASN

A

324

3.633

−69.325

11.013

1.00

125.45

A

C

ATOM

2552

CB

ASN

A

324

2.237

−69.888

11.322

1.00

125.32

A

C

ATOM

2553

CG

ASN

A

324

1.278

−68.832

11.876

1.00

125.29

A

C

ATOM

2554

OD1

ASN

A

324

1.680

−67.915

12.594

1.00

124.69

A

O

ATOM

2555

ND2

ASN

A

324

−0.002

−68.960

11.533

1.00

125.22

A

N

ATOM

2556

C

ASN

A

324

4.559

−70.412

10.480

1.00

126.21

A

C

ATOM

2557

O

ASN

A

324

5.469

−70.840

11.186

1.00

126.38

A

O

ATOM

2558

N

TYR

A

325

4.344

−70.830

9.231

1.00

127.20

A

N

ATOM

2559

CA

TYR

A

325

5.127

−71.914

8.610

1.00

128.15

A

C

ATOM

2560

CB

TYR

A

325

4.484

−72.378

7.295

1.00

128.33

A

C

ATOM

2561

CG

TYR

A

325

5.371

−73.236

6.400

1.00

128.28

A

C

ATOM

2562

CD1

TYR

A

325

5.385

−74.623

6.517

1.00

128.19

A

C

ATOM

2563

CE1

TYR

A

325

6.196

−75.403

5.693

1.00

128.69

A

C

ATOM

2564

CZ

TYR

A

325

7.001

−74.791

4.740

1.00

128.32

A

C

ATOM

2565

OH

TYR

A

325

7.809

−75.546

3.918

1.00

128.32

A

O

ATOM

2566

CE2

TYR

A

325

6.998

−73.419

4.607

1.00

128.03

A

C

ATOM

2567

CD2

TYR

A

325

6.182

−72.652

5.426

1.00

128.22

A

C

ATOM

2568

C

TYR

A

325

6.581

−71.548

8.366

1.00

128.78

A

C

ATOM

2569

O

TYR

A

325

7.457

−72.405

8.457

1.00

128.84

A

O

ATOM

2570

N

PHE

A

326

6.831

−70.288

8.026

1.00

129.74

A

N

ATOM

2571

CA

PHE

A

326

8.196

−69.807

7.856

1.00

130.77

A

C

ATOM

2572

CB

PHE

A

326

8.226

−68.477

7.104

1.00

130.66

A

C

ATOM

2573

CG

PHE

A

326

8.498

−68.634

5.633

1.00

131.15

A

C

ATOM

2574

CD1

PHE

A

326

9.279

−67.709

4.954

1.00

131.45

A

C

ATOM

2575

CE1

PHE

A

326

9.534

−67.857

3.595

1.00

131.35

A

C

ATOM

2576

CZ

PHE

A

326

9.022

−68.953

2.905

1.00

131.18

A

C

ATOM

2577

CE2

PHE

A

326

8.254

−69.894

3.574

1.00

130.77

A

C

ATOM

2578

CD2

PHE

A

326

7.999

−69.733

4.930

1.00

131.24

A

C

ATOM

2579

C

PHE

A

326

8.936

−69.738

9.184

1.00

131.50

A

C

ATOM

2580

O

PHE

A

326

10.052

−70.254

9.305

1.00

131.64

A

O

ATOM

2581

N

SER

A

327

8.299

−69.136

10.184

1.00

132.39

A

N

ATOM

2582

CA

SER

A

327

8.799

−69.202

11.551

1.00

133.35

A

C

ATOM

2583

CB

SER

A

327

8.346

−67.976

12.343

1.00

133.34

A

C

ATOM

2584

OG

SER

A

327

8.873

−66.797

11.762

1.00

133.24

A

O

ATOM

2585

C

SER

A

327

8.380

−70.520

12.228

1.00

133.99

A

C

ATOM

2586

O

SER

A

327

7.698

−70.524

13.255

1.00

134.15

A

O

ATOM

2587

N

SER

A

328

8.785

−71.633

11.618

1.00

134.76

A

N

ATOM

2588

CA

SER

A

328

8.560

−72.981

12.142

1.00

135.55

A

C

ATOM

2589

CB

SER

A

328

7.116

−73.442

11.917

1.00

135.43

A

C

ATOM

2590

OG

SER

A

328

6.926

−73.939

10.604

1.00

135.43

A

O

ATOM

2591

C

SER

A

328

9.540

−73.957

11.491

1.00

136.19

A

C

ATOM

2592

O

SER

A

328

9.619

−75.124

11.875

1.00

136.23

A

O

ATOM

2593

N

LEU

A

329

10.272

−73.471

10.491

1.00

137.16

A

N

ATOM

2594

CA

LEU

A

329

11.387

−74.218

9.910

1.00

138.16

A

C

ATOM

2595

CB

LEU

A

329

11.407

−74.077

8.381

1.00

138.39

A

C

ATOM

2596

CG

LEU

A

329

11.338

−75.401

7.597

1.00

138.89

A

C

ATOM

2597

CD1

LEU

A

329

10.528

−75.238

6.308

1.00

138.84

A

C

ATOM

2598

CD2

LEU

A

329

12.729

−76.000

7.323

1.00

139.11

A

C

ATOM

2599

C

LEU

A

329

12.693

−73.730

10.560

1.00

138.51

A

C

ATOM

2600

O

LEU

A

329

13.787

−74.236

10.275

1.00

138.46

A

O

ATOM

2601

N

LYS

A

330

12.536

−72.734

11.437

1.00

138.95

A

N

ATOM

2602

CA

LYS

A

330

13.549

−72.310

12.400

1.00

139.20

A

C

ATOM

2603

CB

LYS

A

330

13.455

−70.800

12.619

1.00

139.08

A

C

ATOM

2604

CG

LYS

A

330

13.404

−70.002

11.320

1.00

138.84

A

C

ATOM

2605

CD

LYS

A

330

12.923

−68.572

11.529

1.00

138.54

A

C

ATOM

2606

CE

LYS

A

330

14.069

−67.633

11.857

1.00

138.22

A

C

ATOM

2607

NZ

LYS

A

330

13.684

−66.229

11.575

1.00

138.27

A

N

ATOM

2608

C

LYS

A

330

13.339

−73.060

13.725

1.00

139.55

A

C

ATOM

2609

O

LYS

A

330

14.168

−72.985

14.632

1.00

139.50

A

O

ATOM

2610

N

ASN

A

331

12.214

−73.775

13.813

1.00

140.04

A

N

ATOM

2611

CA

ASN

A

331

11.873

−74.659

14.934

1.00

140.56

A

C

ATOM

2612

CB

ASN

A

331

10.355

−74.606

15.173

1.00

140.51

A

C

ATOM

2613

CG

ASN

A

331

9.949

−75.079

16.562

1.00

140.17

A

C

ATOM

2614

OD1

ASN

A

331

9.623

−74.265

17.426

1.00

139.91

A

O

ATOM

2615

ND2

ASN

A

331

9.950

−76.393

16.776

1.00

139.41

A

N

ATOM

2616

C

ASN

A

331

12.314

−76.110

14.639

1.00

140.98

A

C

ATOM

2617

O

ASN

A

331

12.161

−76.568

13.501

1.00

141.01

A

O

ATOM

2618

N

PRO

A

332

12.871

−76.827

15.653

1.00

141.35

A

N

ATOM

2619

CA

PRO

A

332

13.332

−78.222

15.545

1.00

141.44

A

C

ATOM

2620

CB

PRO

A

332

13.057

−78.776

16.949

1.00

141.46

A

C

ATOM

2621

CG

PRO

A

332

13.186

−77.556

17.868

1.00

141.67

A

C

ATOM

2622

CD

PRO

A

332

13.182

−76.301

16.997

1.00

141.45

A

C

ATOM

2623

C

PRO

A

332

12.616

−79.072

14.493

1.00

141.44

A

C

ATOM

2625

OXT

PRO

A

332

13.215

−79.439

13.481

1.00

141.35

A

O

ATOM

2626

NAV

DRG

B

1

−23.713

−62.247

−7.614

1.00

77.69

N

ATOM

2627

CBB

DRG

B

1

−23.360

−63.208

−6.766

1.00

78.09

C

ATOM

2628

CAK

DRG

B

1

−22.301

−63.335

−5.875

1.00

75.97

C

ATOM

2629

CAI

DRG

B

1

−22.187

−64.483

−5.099

1.00

74.06

C

ATOM

2630

CAZ

DRG

B

1

−23.130

−65.498

−5.214

1.00

75.54

C

ATOM

2631

CBO

DRG

B

1

−23.003

−66.759

−4.359

1.00

75.85

C

ATOM

2632

CAD

DRG

B

1

−21.560

−67.259

−4.429

1.00

75.72

C

ATOM

2633

CAE

DRG

B

1

−23.382

−66.419

−2.918

1.00

77.20

C

ATOM

2634

CAC

DRG

B

1

−23.955

−67.819

−4.918

1.00

74.37

C

ATOM

2635

CAM

DRG

B

1

−24.188

−65.368

−6.106

1.00

77.60

C

ATOM

2636

CBC

DRG

B

1

−24.300

−64.220

−6.881

1.00

78.94

C

ATOM

2637

NAW

DRG

B

1

−25.184

−63.832

−7.794

1.00

78.28

N

ATOM

2638

CBA

DRG

B

1

−24.826

−62.628

−8.241

1.00

79.13

C

ATOM

2639

CAN

DRG

B

1

−25.571

−61.816

−9.301

1.00

79.81

C

ATOM

2640

CAO

DRG

B

1

−24.986

−62.063

−10.693

1.00

79.86

C

ATOM

2641

CBG

DRG

B

1

−25.614

−63.300

−11.340

1.00

80.40

C

ATOM

2642

CAQ

DRG

B

1

−24.819

−64.545

−10.941

1.00

78.89

C

ATOM

2643

CAP

DRG

B

1

−25.105

−63.439

−12.776

1.00

79.82

C

ATOM

2644

CBH

DRG

B

1

−24.419

−64.755

−12.403

1.00

78.01

C

ATOM

2645

NBM

DRG

B

1

−22.964

−64.605

−12.540

1.00

75.33

N

ATOM

2646

CBF

DRG

B

1

−22.289

−65.703

−11.833

1.00

73.44

C

ATOM

2647

CAB

DRG

B

1

−22.500

−67.011

−12.599

1.00

71.28

C

ATOM

2648

CAA

DRG

B

1

−20.799

−65.383

−11.695

1.00

73.40

C

ATOM

2649

CAR

DRG

B

1

−22.599

−64.642

−13.964

1.00

70.65

C

ATOM

2650

CBK

DRG

B

1

−22.016

−63.289

−14.377

1.00

65.92

C

ATOM

2651

OAX

DRG

B

1

−20.589

−63.395

−14.485

1.00

64.75

O

ATOM

2652

CBI

DRG

B

1

−22.471

−62.950

−15.798

1.00

64.30

C

ATOM

2653

OAG

DRG

B

1

−23.564

−62.031

−15.743

1.00

65.97

O

ATOM

2654

CBJ

DRG

B

1

−21.254

−62.261

−16.418

1.00

63.34

C

ATOM

2655

OAH

DRG

B

1

−21.588

−60.911

−16.750

1.00

64.58

O

ATOM

2656

CBL

DRG

B

1

−20.216

−62.269

−15.294

1.00

58.52

C

ATOM

2657

N9

DRG

B

1

−18.870

−62.496

−15.866

1.00

51.11

N

ATOM

2658

C8

DRG

B

1

−18.311

−63.682

−16.109

1.00

51.98

C

ATOM

2659

N7

DRG

B

1

−17.095

−63.499

−16.624

1.00

46.56

N

ATOM

2660

C5

DRG

B

1

−16.880

−62.191

−16.710

1.00

39.50

C

ATOM

2661

C4

DRG

B

1

−18.007

−61.552

−16.229

1.00

41.15

C

ATOM

2662

N3

DRG

B

1

−18.045

−60.213

−16.207

1.00

40.98

N

ATOM

2663

C2

DRG

B

1

−17.014

−59.506

−16.641

1.00

44.16

C

ATOM

2664

N1

DRG

B

1

−15.919

−60.086

−17.109

1.00

40.65

N

ATOM

2665

C6

DRG

B

1

−15.818

−61.421

−17.158

1.00

39.87

C

ATOM

2666

N6

DRG

B

1

−14.715

−61.999

−17.628

1.00

45.08

N

END

Claims

1. A compound of Formula (I) below or a pharmaceutically acceptable salt or ester thereof:

2. The compound of claim 1 wherein the R9 is a group such that R9 induces a residence time of the compound greater than 20 seconds in a complex formed of the compound and human DOT1L.

3. The compound of claim 1, wherein the SAM binding pocket of human DOT1L is characterized by the crystallography coordinates of one or more human DOT1L amino acids Val135, Thr139, Asp161, Gly163, Gln168, Glu 186, Asp222, Phe223, and Asn241, according to Table S1 or S2.

4. The compound of claim 1, wherein the hydrophobic pocket domain of human DOT L is characterized by the crystallography coordinates of human DOT L amino acids Leu143, Met147, Phe239, and Tyr312, according to Table S1 or S2.

5. The compound of claim 1, wherein the binding affinity (Ki) of the compound to human DOT1L is not greater than 50 μM.

6. The compound of claim 1, wherein R9 comprises C6-C10 aryl or 5 to 10-membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of unsubstituted or substituted t-butyl, CF3, cyclohexyl, C6-C10 aryl, and 5 to 10-membered heteroaryl.

7. The compound of claim 6, wherein the one or more substituents are t-butyl.

8. The compound of claim 6, wherein R9 is selected from the group consisting of

9. The compound of claim 1, being of formula (II):

10. The compound of claim 9, wherein T is —CH2-L1-L2-L3-, with L3 connected to R9, wherein: L1 is N(Y), S, SO, or SO2;L2 is CO or absent when L1 is N(Y), or L2 is absent when L1 is S, SO, or SO2, in which Y is H, Rd, SO2Rd, or CORd when L2 is absent, or Y is H or Rd when L2 is CO, Rd being C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C5 cycloalkyl, C6-C10 aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and Rd being optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo, carboxyl, cyano, C1-C6 alkoxyl, C1-C6 alkylsulfonyl, C3-C5 cycloalkyl, C6-C10 aryl, 4 to 8-membered heterocycloalkyl, 5 to 6-membered heteroaryl, ORd′, OCORd′, and N(Rd′)2, and with C3-C5 cycloalkyl, C6-C10 aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl further optionally substituted with C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo, hydroxyl, carboxyl, C(O)OH, C(O)O—C1-C6 alkyl, OC(O)—C1-C6 alkyl, cyano, C1-C6 alkoxyl, amino, mono-C1-C6 alkylamino, di-C1-C6 alkylamino, C3-C5 cycloalkyl, C6-C10 aryl, 4 to 6-membered heterocycloalkyl, or 5 to 6-membered heteroaryl; each Rd′ independently being H, C1-C6 alkyl, silyl, C1-C6 alkyl-C3-C5 cycloalkyl, C6-C10 aryl, 5 to 6-membered heteroaryl, aralkyl, or heteroaralkyl;L3 is —(CR4R5)n(CR6R7)m— or —(CR4R5)n-unsubstituted or substituted C3-C8 cycloalkyl-(CR6R7)m—, with (CR6R7)m connected to R9;each of R4, R5, R6, and R7, independently, is H, halo, hydroxyl, carboxyl, cyano, or RS2, RS2 being amino, C1-C6 alkoxyl, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl, and each RS2 being optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, C1-C6 alkoxyl, amino, mono-C1-C6 alkylamino, di-C1-C6 alkylamino, C3-C5 cycloalkyl, C6-C10 aryl, 4 to 6-membered heterocycloalkyl, and 5 to 6-membered heteroaryl; or two geminal R4 and R5 or two geminal R6 and R7 taken together are ethylene, propylene or butylene;m is 0, 1, or 2; andn is 0, 1, or 2.

11. The compound of claim 9, wherein R9 is

12. The compound of claim 10, wherein the compound is of formula (IIIa) or (IIIb):

13. The compound of claim 12, wherein the compound is of formula (IIIa) and R9 is

14. (canceled)

15. A method for the design and identification of a potential binding compound for protein DOT1L comprising the steps of: (a) generating, on a computer, a three-dimensional structure of DOT1L having the structural coordinates of Table S1 or S2;(b) identifying amino acid residues forming an hydrophobic pocket site in the three-dimensional structure of DOT1L from step (a), wherein the hydrophobic pocket domain of DOT1L is characterized by the crystallography coordinates of human DOT1L amino acids Leu143, Met147, Phe239, and Tyr312 according to Table S1 or S2;(c) generating a three-dimensional model of the active site;(d) designing and/or selecting a compound that potentially binds to the active site using the three-dimensional model of the active site; and(e) synthesizing and/or choosing the potential binding compound.

16-18. (canceled)

19. A DOT1L inhibitor having molecular dimensions compatible with the shape of a hydrophobic pocket domain of DOT1L characterized by the crystallography coordinates of human DOT1L amino acids Leu143, Met147, Phe239, and Tyr312, according to Table S1 or S2, wherein the compound has a biochemical IC50 for DOT1L of less than 100 nM.

20-22. (canceled)

23. A method for designing, identifying, and/or optimizing a candidate DOT1L inhibitor compound or complex, the method comprising: (a) generating a crystal structure, a three-dimensional model of DOT1L, or obtaining the structure coordinates of DOT1L in complex with the candidate DOT1L inhibitor compound or complex, and(b) determining if the candidate DOT L inhibitor compound or complex induces a conformational adaptation and/or a hydrophobic binding site of the DOT1L from the three-dimensional model.

24. The method of claim 23, further comprising contacting the identified candidate inhibitor with DOT1L in order to determine the effect of the inhibitor on DOT1L enzymatic activity.

25. (canceled)

26. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

27. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a DOT1L inhibitor designed, identified, and/or optimized by the method of claim 15.

28. A method for treating cancer comprising administrating a therapeutically effective amount of a compound of claim 1 to a subject in need thereof.

29-32. (canceled)