CRYSTALLIZED PPARa LIGAND BINDING DOMAIN POLYPEPTIDE AND SCREENING METHODS EMPLOYING SAME

TECHNICAL FIELD

[0001] The present invention relates generally to the structure of the ligand binding domain of PPARα, and more particularly to the structure of the ligand binding domain of PPARα in complex with a ligand. The invention further relates to methods by which modulators and ligands of PPARα and other PPARs can be identified.

1AbbreviationsATPadenosine triphosphateADPadenosine diphosphateBSAbovine serum albumincDNAcomplementary DNADBDDNA binding domainDMSOdimethyl sulfoxideDNAdeoxyribonucleic acidDTTdithiothreitolEDTAethylenediaminetetraacetic acidHEPESN-2-Hydroxyethylpiperazine-N'-2-ethanesulfonicacidkDakilodalton(s)LBDligand binding domainmPPARmouse peroxisome proliferator activated receptorNDPnucleotide diphosphateNTPnucleotide triphosphatePAGEpolyacrylamide gel electrophoresisPCRpolymerase chain reactionplisoelectric pointPPARperoxisome proliferator-activated receptorPPARαperoxide proliferator-activated receptor alphaPPREPPAR response elementrPPARrat peroxisome proliferator activated receptorRXRretinoid X receptorSDSsodium dodecyl sulfateSDS-PAGEsodium dodecyl sulfate polyacrylamide gelelectrophoresis

[0002]

2

Amino Acid Abbreviations

Single-Letter Code
Three-Letter Code
Name

A
Ala
Alanine

V
Val
Valine

L
Leu
Leucine

I
Ile
Isoleucine

P
Pro
Proline

F
Phe
Phenylalanine

W
Trp
Tryptophan

M
Met
Methionine

G
Gly
Glycine

S
Ser
Serine

T
Thr
Threonine

C
Cys
Cysteine

Y
Tyr
Tyrosine

N
Asn
Asparagine

Q
Gln
Glutamine

D
Asp
Aspartic Acid

E
Glu
Glutamic Acid

K
Lys
Lysine

R
Arg
Arginine

H
His
Histidine

[0003]

3

Functionally Equivalent Codons

Amino Acid
Codons

Alanine
Ala
A
GCA GCC GCG GCU

Cysteine
Cys
C
UGC UGU

Aspartic Acid
Asp
0
GAC GAU

Glumatic acid
Glu
E
GAA GAG

Phenylalanine
Phe
F
UUC UUU

Glycine
Gly
G
GGA GGC GGG GGU

Histidine
His
H
CAC CAU

Isoleucine
lie
I
AUA AUC AUU

Lysine
Lys
K
AAA AAG

Methionine
Met
M
AUG

Asparagine
Asn
N
AAC AAU

Proline
Pro
P
CCA CCC CCG CCU

Glutamine
GIn
Q
CAA GAG

Threonine
Thr
T
ACA ACC ACG ACU

Valine
Val
V
GUA GUC GUG GUU

Tryptophan
Trp
W
UGG

Tyrosine
Tyr
Y
UAC UAU

Leucine
Leu
L
UUA UUG CUA CUC

CUG CUU

Arginine
Arg
R
AGA AGG OGA CGC

CGG CGU

Serine
Ser
S
ACG AGU UCA UCC

UCG UCU

BACKGROUND ART

[0004] Nuclear receptors reside in either the cytoplasm or nucleus of eukaryotic cells and represent a superfamily of proteins that specifically bind a physiologically relevant small molecule, such as a hormone or vitamin. As a result of a molecule binding to a nuclear receptor, the nuclear receptor changes the ability of a cell to transcribe DNA, i.e. nuclear receptors modulate the transcription of DNA. However, they can also have transcription independent actions.

[0005] Unlike integral membrane receptors and membrane-associated receptors, nuclear receptors reside in either the cytoplasm or nucleus of eukaryotic cells. Thus, nuclear receptors comprise a class of intracellular, soluble, ligand-regulated transcription factors. Nuclear receptors include but are not limited to receptors for glucocorticoids, androgens, mineralcorticoids, progestins, estrogens, thyroid hormones, vitamin D, retinoids, icosanoids and pertinently, peroxisome proliferators. Many nuclear receptors, identified by either sequence homology to known receptors (See, e.g., Drewes et al., (1996) Mol. Cell. Biol. 16:925-31) or based on their affinity for specific DNA binding sites in gene promoters (See, e.g., Sladek et al., Genes Dev. 4:2353-65), have unascertained ligands and are therefore termed “orphan receptors”.

[0006] Peroxisomes are organelles that are involved in the β-oxidation of long-chain fatty acids and the catabolism of cholesterol to bile acids (See, e.g., Vamecq & Draye, (1989) Essays Biochem. 24: 115-225). Peroxisome proliferators are a structurally diverse group of compounds which, when administered to rodents, elicit dramatic increases in the size and number of hepatic and renal peroxisomes, as well as concomitant increases in the capacity of peroxisomes to metabolize fatty acids via increased expression of the enzymes required for the β-oxidation cycle (Lazarow & Fujiki, (1985) Ann. Rev. Cell Biol. 1: 489-530; Vamecq & Draye, (1989) Essays Biochem. 24: 115-225; and Nelali et al., (1988) Cancer Res. 48: 5316-5324). Chemicals of this group include the fibrate class of hypolipidermic drugs, herbicides, phthalate plasticizers, unsaturated fatty acids, and leukotriene antagonists (reviewed in Green, (1992) Biochem. Pharmacol. 43: 393-401). Peroxisome proliferation can also be elicited by dietary or physiological factors such as a high-fat diet and cold acclimatization.

[0007] Peroxisome proliferator activated receptors (PPARs) are activated by one of a group of compounds known as peroxisome proliferators. Insight into the mechanism by which peroxisome proliferators exert their pleiotropic effects was provided by the identification of a member of the nuclear hormone receptor superfamily activated by the chemicals described above (Isseman & Green, (1990) Nature 347: 645-50). This receptor, termed peroxisome proliferator activated receptor alpha (PPARα), was subsequently shown to be activated by a variety of medium and long-chain fatty acids. PPARα was also shown to modulate expression of a variety of genes containing one or more PPAR responsive elements found in their promoter regions.

[0008] It appears that PPARα has a role in the regulation of virtually the entire oxidative pathway of fatty acids and their derivatives (See, Lemberger et al., (1996) Ann. Rev. Cell. Dev. Biol. 12: 335-63). It has also been observed that PPARα expression is closely tied to conditions that induce elevated glucocorticoid levels such as fasting, diurnal rhythm (Lemberger et al., (1996) J. Biol. Chem. 271: 1764-69) and stress.

[0009] Structurally, PPARα comprises three functional domains, the N terminus region, the DNA binding domain and the ligand binding domain. These domains retain their functional autonomy when they are expressed as a chimeric or fusion protein (Göttlicher et al., (1992) Proc. Natl. Acad. Sci. U.S.A. 89: 4653-57).

[0010] PPARα activates transcription by binding to DNA sequence elements, termed PPAR response elements (PPRE), as heterodimers (dimerization is essential for the activity of PPARs) with the retinoid X receptors (RXR) (See, Keller & Whali, (1993) Trends Endocrin. Met. 4: 291-96), which are themselves activated by 9-cis retinoic acid (See, Kliewer et al., (1992) Nature 358: 771-74; Gearing et al., (1993) Proc. Natl. Acad. Sci. U.S.A. 90: 1440-44; Keller et al., (1993) Proc. Natl. Acad. Sci. U.S.A. 90: 2160-2164; Heyman et al., (1992) Cell 68: 397-406 and Levin et al., (1992) Nature 355: 359-61). Since the PPARα-RXR complex can be activated by peroxisome proliferators and/or 9-cis retinoic acid, the retinoid and fatty acid signaling pathways are seen to converge in modulating lipid metabolism.

[0011] PPREs have been identified in the enhancers of a number of genes that encode proteins that regulate lipid metabolism, including: (1) the three enzymes required for peroxisomal β-oxidation of fatty acids; (2) medium-chain acyl-CoA dehydrogenase, a key enzyme in mitochondrial β-oxidation; and (3) aP2, a lipid binding protein expressed exclusively in adipocytes. Thus, the nature of the PPAR target genes coupled with the activation of PPARs by fatty acids and hypolipidemic drugs suggests a physiological role for the PPARs in a variety of physiological phenomena, including lipid homeostasis (See, e.g., Keller & Whali, (1993) Trends Endocrin. Met. 4: 291-96). PPARs have also been implicated in glucose homeostasis disorders and in atherosclerosis. These conditions may exist alone or together in a complex phenotype of metabolic disorders known as syndrome X.

[0012] Since the discovery of PPARα, additional subtypes of PPAR have been identified, e.g. PPARγ and PPARδ, which are spatially differentially expressed. Because there are several subtypes of PPAR, it is desirable to identify compounds that are capable of selectively interacting with only one of the PPAR subtypes, notably PPARα. Compounds capable of interacting with PPARα exclusively would find a wide variety of applications, for example, in the prevention of obesity, for the treatment of diabetes, and other deleterious conditions, as noted above. Development of such compounds, however, has been hindered by a lack of detailed structural information on the ligand binding domain of PPARα and particularly by a lack of structural information on the conformation of the ligand binding domain of PPARα as it binds a modulating compound.

[0013] It is believed that PPARα regulates some of the same genes as PPARγ and PPARδ. However, some genes might be upregulated by one PPAR and downregulated by another PPAR. Up- or down-regulation of certain genes by a PPARγ agonist might cause detrimental side effects. It might be possible to use a PPARα or PPARδ agonist, partial agonist or antagonist to down- or up-regulate (respectively) these same genes, and thereby reduce the detrimental side-effects. More generally, it might be possible to individually up- and down-regulate specific genes to achieve a specific therapeutic goal by administering a PPAR activator (or partial activator) that activates (or deactivates) each PPAR to the appropriate extent. Design or discovery of such a compound would be greatly facilitated by three-dimensional structures for each of the three target receptors, PPARα, PPARγ and PPARδ.

[0014] Polypeptides, including the ligand binding domain of PPARα, have a three-dimensional structure determined by the primary amino acid sequence and the environment surrounding the polypeptide. This three-dimensional structure establishes the polypeptide's activity, stability, binding affinity, binding specificity, and other biochemical attributes. Thus, knowledge of a protein's three-dimensional structure can provide much guidance in designing agents that mimic, inhibit, or improve its biological activity.

[0015] The three-dimensional structure of a polypeptide can be determined in a number of ways. Many of the most precise methods employ X-ray crystallography (See, e.g., Van Holde, (1971) Physical Biochemistry, Prentice-Hall, N.J., 221-39). This technique relies on the ability of crystalline lattices to diffract X-rays or other forms of radiation. Diffraction experiments suitable for determining the three-dimensional structure of macromolecules typically require high-quality crystals. Unfortunately, such crystals have been unavailable for the ligand binding domain of PPARα, as well as many other proteins of interest. Thus, high-quality diffracting crystals of the ligand binding domain of PPARα in complex with a ligand would greatly assist in the elucidation of its three-dimensional structure.

[0016] Clearly, the solved crystal structure of the PPARα ligand binding domain polypeptide would be useful in the design of modulators of activity mediated by all of the PPARs. Evaluation of the available sequence data has made it clear that PPARα shares significant sequence homology with the other PPARs. Further, PPARα shows structural homology with the three-dimensional fold of the other PPARs. Thus, in theory, it might be considered feasible to design modulators of PPARα based exclusively on the sequence and three-dimensional fold of a different PPAR, for example, PPARγ. This method, however, would likely be unproductive and certainly hindered by a lack of subtle structural details of the various binding sites and pertinent residues of PPARα involved in the binding event. A solved crystal structure would provide these structural details.

[0017] The solved PPARα-ligand crystal structure would provide structural details and insights necessary to design a modulator of PPARα that maximizes preferred requirements for any modulator, i.e. potency and specificity. By exploiting the structural details obtained from a PPAR-ligand crystal structure, it would be possible to design a PPAR modulator that, despite PPARα's similarity with other PPARs, exploits the unique structural features of PPARα. A PPAR modulator developed using structure-assisted design would take advantage of heretofore unknown PPAR structural considerations and thus be more effective than a modulator developed using homology-based design. Potential or existent homology models cannot provide the necessary degree of specificity. A PPAR modulator designed using the structural coordinates of a crystalline form of PPARα would also provide a starting point for the development of modulators of other PPARs.

[0018] What is needed, therefore, is a crystallized form of a PPARα ligand binding domain, preferably in complex with a ligand. Acquisition of crystals of the PPARα ligand binding domain (LBD) polypeptide will permit the three dimensional structure of PPARα LBD polypeptide to be determined. Knowledge of the three dimensional structure will facilitate the design of modulators of PPARα activity. Such modulators can lead to therapeutic compounds to treat a wide range of conditions, including lipid homeostasis disorders, glucose homeostasis disorders, inflammation, atherosclerosis and syndrome X.

SUMMARY OF THE INVENTION

[0019] A substantially pure PPARα ligand binding domain polypeptide in crystalline form is disclosed. Preferably, the crystalline form has lattice constants of a=61.3 Å, b=103.5 Å, c=49.9 Å, α=90°, β=90°, γ=90° or lattice constants of a=95.58 Å, b=122.06 Å, c=122.10 Å, α=90°, β=90°, γ=90°. Preferably, the crystalline form is an orthorhombic crystalline form. More preferably, the crystalline form has a space group of P21212 or space group P212121. Even more preferably, the PPARα ligand binding domain polypeptide has the amino acid sequence shown in SEQ ID NO: 4. Even more preferably, the PPARα ligand binding domain has a crystalline structure further characterized by the coordinates corresponding to Table 2.

[0020] Preferably, the PPARα ligand binding domain polypeptide is in complex with a ligand. Optionally, the crystalline form contains one or four PPARα ligand binding domain polypeptides in the asymmetric unit. Preferably, the crystalline form is such that the three-dimensional structure of the crystallized PPARα ligand binding domain polypeptide can be determined to a resolution of about 1.8 Å or better. Even more preferably, the crystalline form contains one or more atoms having a molecular weight of 40 grams/mol or greater.

[0021] A method for determining the three-dimensional structure of a crystallized PPARα ligand binding domain polypeptide to a resolution of about 1.8 Å or better is disclosed. The method comprises (a) crystallizing a PPARα ligand binding domain polypeptide; and (b) analyzing the PPARα ligand binding domain polypeptide to determine the three-dimensional structure of the crystallized PPARα ligand binding domain polypeptide, whereby the three-dimensional structure of a crystallized PPARα ligand binding domain polypeptide is determined to a resolution of about 1.8 Å or better. Preferably, the analyzing is by X-ray diffraction. More preferably, the crystallization is accomplished by the hanging drop vapor diffusion method, and wherein the PPARα ligand binding domain is mixed with an equal volume of reservoir. Even more preferably, the reservoir comprises 4-8% PEG 3350, 100-200 mM NaF, and 12-16% 2,5 hexanediol or the reservoir comprises 50 mM bis-tris-propane, 4-6% PEG 3350, 150 mM NaNO3, 16% 2,5 hexanediol, and 1-3 mM YCI3.

[0022] A method of designing a modulator of a PPAR polypeptide is disclosed. The method comprises (a) designing a potential modulator of a PPAR polypeptide that will form bonds with amino acids in a substrate binding site based upon a crystalline structure of a PPARα ligand binding domain polypeptide; (b) synthesizing the modulator; and (c) determining whether the potential modulator modulates the activity of the PPAR polypeptide, whereby a modulator of a PPAR polypeptide is designed.

[0023] A method of designing a modulator that selectively modulates the activity of a PPAR polypeptide is disclosed. The method comprises (a) obtaining a crystalline form of a PPARα ligand binding domain polypeptide; (b) evaluating the three-dimensional structure of the crystallized PPARα ligand binding domain polypeptide; and (c) synthesizing a potential modulator based on the three-dimensional crystal structure of the crystallized PPARα ligand binding domain polypeptide, whereby a modulator that selectively modulates the activity of a PPARα polypeptide is designed. Preferably, the method further comprises contacting a PPARα ligand binding domain polypeptide with the potential modulator; and assaying the PPARα ligand binding domain polypeptide for binding of the potential modulator, for a change in activity of the PPARα ligand binding domain polypeptide, or both. More preferably, the crystalline form is in orthorhombic form. Even more preferably, the crystals are such that the three-dimensional structure of the crystallized PPARα ligand binding domain polypeptide can be determined to a resolution of about 1.8 Å or better.

[0024] A method of screening a plurality of compounds for a modulator of a PPAR ligand binding domain polypeptide is disclosed. The method comprises (a) providing a library of test samples; (b) contacting a crystalline PPARα ligand binding domain polypeptide with each test sample; (c) detecting an interaction between a test sample and the crystalline PPARα ligand binding domain polypeptide; (d) identifying a test sample that interacts with the crystalline PPARα ligand binding domain polypeptide; and (e) isolating a test sample that interacts with the crystalline PPARα ligand binding domain polypeptide, whereby a plurality of compounds is screened for a modulator of a PPAR ligand binding domain polypeptide. Preferably, the test samples are bound to a substrate, and more preferably, the test samples are synthesized directly on a substrate.

[0025] A method for identifying a PPAR modulator is disclosed. The method comprises (a) providing atomic coordinates of a PPARα ligand binding domain to a computerized modeling system; and (b) modeling ligands that fit spatially into the binding pocket of the PPARα ligand binding domain to thereby identify a PPAR modulator. Preferably, the method further comprises identifying in an assay for PPAR-mediated activity a modeled ligand that increases or decreases the activity of the PPAR.

[0026] A method of identifying a PPARα modulator that selectively modulates the activity of a PPARα polypeptide compared to other polypeptides is disclosed. The method comprises (a) providing atomic coordinates of a PPARα ligand binding domain to a computerized modeling system; and (b) modeling a ligand that fits into the binding pocket of a PPARα ligand binding domain and that interacts with conformationally constrained residues of a PPARα conserved among PPAR subtypes to thereby identify a PPARα modulator. Preferably, the method further comprises identifying in a biological assay for PPARα activity a modeled ligand that selectively binds to PPARα and increases or decreases the activity of said PPARα.

[0027] A method of designing a modulator of a PPAR polypeptide is disclosed. The method comprises (a) selecting a candidate PPAR ligand; (b) determining which amino acid or amino acids of a PPAR polypeptide interact with the ligand using a three-dimensional model of a crystallized protein comprising a PPARα LBD; (c) identifying in a biological assay for PPAR activity a degree to which the ligand modulates the activity of the PPAR polypeptide; (d) selecting a chemical modification of the ligand wherein the interaction between the amino acids of the PPAR polypeptide and the ligand is predicted to be modulated by the chemical modification; (e) performing the chemical modification on the ligand to form a modified ligand; (f) contacting the modified ligand with the PPAR polypeptide; (g) identifying in a biological assay for PPAR activity a degree to which the modified ligand modulates the biological activity of the PPAR polypeptide; and (h) comparing the biological activity of the PPAR polypeptide in the presence of modified ligand with the biological activity of the PPAR polypeptide in the presence of the unmodified ligand, whereby a modulator of a PPAR polypeptide is designed. Preferably, the PPAR polypeptide is a PPARα polypeptide. More preferably, the three-dimensional model of a crystallized protein is a PPARα LBD polypeptide with a bound ligand. Optionally, the method further comprises repeating steps (a) through (f), if the biological activity of the PPAR polypeptide in the presence of the modified ligand varies from the biological activity of the PPAR polypeptide in the presence of the unmodified ligand.

[0028] An assay method for identifying a compound that inhibits binding of a ligand to a PPAR polypeptide is disclosed. The assay method comprises (a) incubating a PPAR polypeptide with a ligand in the presence of a test inhibitor compound; (b) determining an amount of ligand that is bound to the PPAR polypeptide, wherein decreased binding of ligand to the PPAR protein in the presence of the test inhibitor compound relative to binding of ligand in the absence of the test inhibitor compound is indicative of inhibition; and (c) identifying the test compound as an inhibitor of ligand binding if decreased ligand binding is observed.

[0029] A method of identifying a PPAR modulator that selectively modulates the biological activity of one PPAR subtype compared to PPARα is disclosed. The method comprises: (a) providing an atomic structure coordinate set describing a PPARα ligand binding domain structure and at least one other atomic structure coordinate set describing a PPAR ligand binding domain, each ligand binding domain comprising a ligand binding site; (b) comparing the PPAR atomic structure coordinate sets to identify at least one difference between the sets; (c) designing a candidate ligand predicted to interact with the difference of step (b); (d) synthesizing the candidate ligand; and (e) testing the synthesized candidate ligand for an ability to selectively modulate a PPAR subtype as compared to PPARα, whereby a PPAR modulator that selectively modulates the biological activity of one PPAR subtype compared to PPARα is identified.

[0030] Accordingly, it is an object of the present invention to provide a three dimensional structure of the ligand binding domain of PPARα. The object is achieved in whole or in part by the present invention.

[0031] An object of the invention having been stated hereinabove, other objects will be evident as the description proceeds, when taken in connection with the accompanying Drawings and Laboratory Examples as best described hereinbelow.

BRIEF DESCRIPTION OF THE DRAWINGS

[0032]
FIG. 1 is a ribbon diagram depicting the PPARα LBD in complex with Compound 1. The PPARα LBD is presented as a ribbon diagram and Compound 1 is presented as a spacefilling model.

[0033]
FIG. 2 is a schematic drawing depicting interactions between PPARα and Compound 1. Residues that lie within 5.5 Å of heavy atoms in the ligand are shown.

[0034]
FIG. 3 depicts overlayed ball and stick diagrams of PPARα, PPARγ and PPARδ. PPARα is shown in dark gray, PPARγ in medium gray and PPARδ in light gray. PPARδ was used as a template in the molecular replacement solution of PPARα.

[0035]
FIG. 4 is a ribbon diagram of the PPARα backbone conformation, where the ligand binding pocket of PPARα is identified by a smooth solid surface.

[0036]
FIG. 5 is a ribbon diagram of the PPARγ backbone conformation, where the ligand binding pocket of PPARγ is identified by a smooth solid surface.

[0037]
FIG. 6 is a ribbon diagram of the PPARδ backbone conformation, where the ligand binding pocket of PPARδ is identified by a smooth solid surface.

[0038]
FIG. 7 is a ball-and-stick model depicting hydrogen bonding interactions between Compound 1 and PPARα. Water molecules are shown as octahedral (six-pointed) crosses.

DETAILED DESCRIPTION OF THE INVENTION

[0039] Until disclosure of the present invention presented herein, the ability to obtain crystalline forms of a PPARα LBD has not been realized. And until disclosure of the present invention presented herein, a detailed three-dimensional crystal structure of a PPARα polypeptide has not been solved.

[0040] In addition to providing structural information, crystalline polypeptides provide other advantages. For example, the crystallization process itself further purifies the polypeptide, and satisfies one of the classical criteria for homogeneity. In fact, crystallization frequently provides unparalleled purification quality, removing impurities that are not removed by other purification methods such as HPLC, dialysis, conventional column chromatography, etc. Moreover, crystalline polypeptides are often stable at ambient temperatures and free of protease contamination and other degradation associated with solution storage. Crystalline polypeptides can also be useful as pharmaceutical preparations. Finally, crystallization techniques in general are largely free of problems such as denaturation associated with other stabilization methods (e.g., lyophilization). Once crystallization has been accomplished, crystallographic data provides useful structural information that can assist the design of compounds that can serve as agonists or antagonists, as described herein below. In addition, the crystal structure provides information useful to map a receptor binding domain, which could then be mimicked by a small non-peptide molecule that would serve as an antagonist or agonist.

I. Definitions

[0041] Following long-standing patent law convention, the terms “a” and “an” mean “one or more” when used in this application, including the claims.

[0042] As used herein, the term “mutation” carries its traditional connotation and means a change, inherited, naturally occurring or introduced, in a nucleic acid or polypeptide sequence, and is used in its sense as generally known to those of skill in the art.

[0043] As used herein, the term “labeled” means the attachment of a moiety, capable of detection by spectroscopic, radiologic or other methods, to a probe molecule.

[0044] As used herein, the term “target cell” refers to a cell, into which it is desired to insert a nucleic acid sequence or polypeptide, or to otherwise effect a modification from conditions known to be standard in the unmodified cell. A nucleic acid sequence introduced into a target cell can be of variable length. Additionally, a nucleic acid sequence can enter a target cell as a component of a plasmid or other vector or as a naked sequence.

[0045] As used herein, the term “transcription” means a cellular process involving the interaction of an RNA polymerase with a gene that directs the expression as RNA of the structural information present in the coding sequences of the gene. The process includes, but is not limited to the following steps: (a) the transcription initiation, (b) transcript elongation, (c) transcript splicing, (d) transcript capping, (e) transcript termination, (f) transcript polyadenylation, (g) nuclear export of the transcript, (h) transcript editing, and (i) stabilizing the transcript.

[0046] As used herein, the term “expression” generally refers to the cellular processes by which a biologically active polypeptide is produced.

[0047] As used herein, the term “transcription factor” means a cytoplasmic or nuclear protein which binds to such gene, or binds to an RNA transcript of such gene, or binds to another protein which binds to such gene or such RNA transcript or another protein which in turn binds to such gene or such RNA transcript, so as to thereby modulate expression of the gene. Such modulation can additionally be achieved by other mechanisms; the essence of “transcription factor for a gene” is that the level of transcription of the gene is altered in some way.

[0048] As used herein, the term “hybridization” means the binding of a probe molecule, a molecule to which a detectable moiety has been bound, to a target sample.

[0049] As used herein, the term “detecting” means confirming the presence of a target entity by observing the occurrence of a detectable signal, such as a radiologic or spectroscopic signal that will appear exclusively in the presence of the target entity.

[0050] As used herein, the term “sequencing” means the determining the ordered linear sequence of nucleic acids or amino acids of a DNA or protein target sample, using conventional manual or automated laboratory techniques.

[0051] As used herein, the term “isolated” means oligonucleotides substantially free of other nucleic acids, proteins, lipids, carbohydrates or other materials with which they can be associated, such association being either in cellular material or in a synthesis medium. The term can also be applied to polypeptides, in which case the polypeptide will be substantially free of nucleic acids, carbohydrates, lipids and other undesired polypeptides.

[0052] As used herein, the term “substantially pure” means that the polynucleotide or polypeptide is substantially free of the sequences and molecules with which it is associated in its natural state, and those molecules used in the isolation procedure. The term “substantially free” means that the sample is at least 50%, preferably at least 70%, more preferably 80% and most preferably 90% free of the materials and compounds with which is it associated in nature.

[0053] As used herein, the term “primer” means a sequence comprising two or more deoxyribonucleotides or ribonucleotides, preferably more than three, and more preferably more than eight and most preferably at least about 20 nucleotides of an exonic or intronic region. Such oligonucleotides are preferably between ten and thirty bases in length.

[0054] As used herein, the term “gene” is used for simplicity to refer to a functional protein, polypeptide or peptide encoding unit. As will be understood by those in the art, this functional term includes both genomic sequences and cDNA sequences. Preferred embodiments of genomic and cDNA sequences are disclosed herein.

[0055] As used herein, the term “DNA segment” means a DNA molecule that has been isolated free of total genomic DNA of a particular species. In a preferred embodiment, a DNA segment encoding a PPARα polypeptide refers to a DNA segment that comprises SEQ ID NOs: 1 and 3, but can optionally comprise fewer or additional nucleic acids, yet is isolated away from, or purified free from, total genomic DNA of a source species, such as Homo sapiens. Included within the term “DNA segment” are DNA segments and smaller fragments of such segments, and also recombinant vectors, including, for example, plasmids, cosmids, phages, viruses, and the like.

[0056] As used herein, the phrase “enhancer-promoter” means a composite unit that contains both enhancer and promoter elements. An enhancer-promoter is operatively linked to a coding sequence that encodes at least one gene product.

[0057] As used herein, the phrase “operatively linked” means that an enhancer-promoter is connected to a coding sequence in such a way that the transcription of that coding sequence is controlled and regulated by that enhancer-promoter. Techniques for operatively linking an enhancer-promoter to a coding sequence are well known in the art; the precise orientation and location relative to a coding sequence of interest is dependent, inter alia, upon the specific nature of the enhancer-promoter.

[0058] As used herein, the terms “candidate substance” and “candidate compound” are used interchangeably and refer to a substance that is believed to interact with another moiety, for example a given ligand that is believed to interact with a complete, or a fragment of, a PPAR polypeptide, and which can be subsequently evaluated for such an interaction. Representative candidate substances or compounds include xenobiotics such as drugs and other therapeutic agents, carcinogens and environmental pollutants, natural products and extracts, as well as endobiotics such as steroids, fatty acids and prostaglandins. Other examples of candidate compounds that can be investigated using the methods of the present invention include, but are not restricted to, agonists and antagonists of a PPAR polypeptide, toxins and venoms, viral epitopes, hormones (e.g., opioid peptides, steroids, etc.), hormone receptors, peptides, enzymes, enzyme substrates, co-factors, lectins, sugars, oligonucleotides or nucleic acids, oligosaccharides, proteins, small molecules and monoclonal antibodies.

[0059] As used herein, the term “biological activity” means any observable effect flowing from interaction between a PPAR polypeptide and a ligand. Representative, but non-limiting, examples of biological activity in the context of the present invention include dimerization of PPARα with RXR, phosphorylation, and association of PPARα with DNA.

[0060] As used herein, the term “modified” means an alteration from an entity's normally occurring state. An entity can be modified by removing discrete chemical units or by adding discrete chemical units. The term “modified” encompasses detectable labels as well as those entities added as aids in purification.

[0061] As used herein, the terms “structure coordinates” and “structural coordinates” mean mathematical coordinates derived from mathematical equations related to the patterns obtained on diffraction of a monochromatic beam of X-rays by the atoms (scattering centers) of a molecule in crystal form. The diffraction data are used to calculate an electron density map of the repeating unit of the crystal. The electron density maps are used to establish the positions of the individual atoms within the unit cell of the crystal.

[0062] Those of skill in the art understand that a set of structure coordinates determined by X-ray crystallography is not without standard error. For the purpose of this invention, any set of structure coordinates for PPARα or a PPARα mutant that have a root mean square (RMS) deviation of no more than 1.0 Å when superimposed, using the polypeptide backbone atoms, on the structure coordinates listed in Table 2 shall be considered identical.

[0063] As used herein, the term “space group” means the arrangement of symmetry elements of a crystal.

[0064] As used herein, the term “molecular replacement” means a method that involves generating a preliminary model of the wild-type PPARα ligand binding domain, or a PPARα mutant crystal whose structure coordinates are unknown, by orienting and positioning a molecule whose structure coordinates are known (e.g., PPARδ) within the unit cell of the unknown crystal so as best to account for the observed diffraction pattern of the unknown crystal. Phases can then be calculated from this model and combined with the observed amplitudes to give an approximate Fourier synthesis of the structure whose coordinates are unknown. This, in turn, can be subject to any of the several forms of refinement to provide a final, accurate structure of the unknown crystal. (Lattman, (1985) Method Enzymol., 115: 55-77; Rossmann, ed, (1972) The Molecular Replacement Method, Gordon & Breach, New York.) Using the structure coordinates of the ligand binding domain of PPARα provided by this invention, molecular replacement can be used to determine the structure coordinates of a crystalline mutant or homologue of the PPARα ligand binding domain, or of a different crystal form of the PPARα ligand binding domain.

[0065] As used herein, the terms “β-sheet” and “beta-sheet” mean the conformation of a polypeptide chain stretched into an extended zig-zig conformation. Portions of polypeptide chains that run “parallel” all run in the same direction. Polypeptide chains that are “antiparallel” run in the opposite direction from the parallel chains.

[0066] As used herein, the terms “α-helix” and “alpha-helix” mean the conformation of a polypeptide chain wherein the polypeptide backbone is wound around the long axis of the molecule in a left-handed or right-handed direction, and the R groups of the amino acids protrude outward from the helical backbone, wherein the repeating unit of the structure is a single turnoff the helix, which extends about 0.56 nm along the long axis.

[0067] As used herein, the term “unit cell” means a basic parallelipiped shaped block. The entire volume of a crystal can be constructed by regular assembly of such blocks. Each unit cell comprises a complete representation of the unit of pattern, the repetition of which builds up the crystal. Thus, the term “unit cell” means the fundamental portion of a crystal structure that is repeated infinitely by translation in three dimensions. A unit cell is characterized by three vectors a, b, and c, not located in one plane, which form the edges of a parallelepiped. Angles α, β and γ define the angles between the vectors: angle α is the angle between vectors b and c; angle β is the angle between vectors a and c; and angle γ is the angle between vectors a and b. The entire volume of a crystal can be constructed by regular assembly of unit cells; each unit cell comprises a complete representation of the unit of pattern, the repetition of which builds up the crystal.

[0068] As used herein, “orthorhombic unit cell” means a unit cell wherein a≠b≠c; and α=β=γ=90°. The vectors a, b and c describe the unit cell edges and the angles α, β, and γ describe the unit cell angles.

[0069] As used herein, the term “crystal lattice” means the array of points defined by the vertices of packed unit cells.

[0070] As used herein, the term “PPAR” means any polypeptide sequence that can be aligned with at least one of human PPARα, PPARγ or PPARδ such that at least 50% of the amino acids are identical to the corresponding amino acid in the human PPARα, PPARγ or PPARδ. The term “PPAR” also encompasses nucleic acid sequences where the corresponding translated protein sequence can be considered to be a PPAR. The term “PPAR” encompasses at least the PPARα, PPARγ and PPARδ subtypes. The term “PPAR” includes invertebrate homologs; preferably, PPAR nucleic acids and polypeptides are isolated from eukaryotic sources. “PPAR” further includes vertebrate homologs of PPAR family members, including, but not limited to, mammalian and avian homolog. Representative mammalian homologs of PPAR family members include, but are not limited to, murine and human homologs.

[0071] As used herein, the terms “PPARα gene product”, “PPARα protein”, “PPARα polypeptide”, and “PPARα peptide” are used interchangeably and mean peptides having amino acid sequences which are substantially identical to native amino acid sequences from the organism of interest and which are biologically active in that they comprise all or a part of the amino acid sequence of a PPARα polypeptide, or cross-react with antibodies raised against a PPARα polypeptide, or retain all or some of the biological activity (e.g., DNA or ligand binding ability and/or dimerization ability) of the native amino acid sequence or protein. Such biological activity can include immunogenicity.

[0072] In the present invention, the terms “PPARα gene product”, “PPARα protein”, “PPARα polypeptide”, and “PPARα peptide” are used interchangeably and mean to the preferred subtype of the PPAR family, namely PPARα, which comprises the amino acid sequence of SEQ ID NO: 2.

[0073] As used herein, the terms “PPARα gene product”, “PPARα protein”, “PPARα polypeptide”, and “PPARα peptide” also include analogs of a PPARα polypeptide. By “analog@ is intended that a DNA or peptide sequence can contain alterations relative to the sequences disclosed herein, yet retain all or some of the biological activity of those sequences. Analogs can be derived from genomic nucleotide sequences as are disclosed herein or from other organisms, or can be created synthetically. Those skilled in the art will appreciate that other analogs, as yet undisclosed or undiscovered, can be used to design and/or construct PPARα analogs. There is no need for a “PPARα gene product”, “PPARα protein”, “PPARα polypeptide”, or “PPARα peptide” to comprise all or substantially all of the amino acid sequence of a PPARα polypeptide gene product. Shorter or longer sequences are anticipated to be of use in the invention; shorter sequences are herein referred to as “segments”. Thus, the terms “PPARα gene product”, “PPARα protein”, “PPARα polypeptide”, and “PPARα peptide” also include fusion or recombinant PPARα polypeptides and proteins comprising sequences of the present invention. Methods of preparing such proteins are disclosed herein and are known in the art.

[0074] As used herein, the term “polypeptide” means any polymer comprising any of the 20 protein amino acids, regardless of its size. Although “protein” is often used in reference to relatively large polypeptides, and “peptide” is often used in reference to small polypeptides, usage of these terms in the art overlaps and varies. The term “polypeptide” as used herein refers to peptides, polypeptides and proteins, unless otherwise noted. As used herein, the terms “protein”, “polypeptide” and “peptide” are used interchangeably herein when referring to a gene product.

[0075] As used herein, the term “modulate” means an increase, decrease, or other alteration of any or all chemical and biological activities or properties of a wild-type or mutant PPAR polypeptide, preferably a wild-type or mutant PPARα polypeptide. The term “modulation” as used herein refers to both upregulation (i.e., activation or stimulation) and downregulation (i.e. inhibition or suppression) of a response.

[0076] As used herein, the terms “binding pocket of the PPARα ligand binding domain”, “PPARα ligand binding pocket” and “PPARα binding pocket” are used interchangeably, and refer to the large cavity within the PPARα ligand binding domain where Compound 1 binds. This cavity may be empty, or may contain water molecules or other molecules from the solvent, or may contain ligand atoms. The “main” binding pocket includes the region of space not occupied by atoms of PPARα that comprises residues Ile-241, Leu-247, Ala-250, Glu-251, Leu-254, Val-255, Ile-272, Phe-273, Cys-275, Cys-276, Gln-277, Thr-279, Ser-280, Tyr-314, Ile-317, Phe-318, Leu-321, Met-330, Val-332, Ala-333, Ile-339, Leu-344, Ile-354, Met-355, His-440, Val-444, Leu-456, Leu-460 and Tyr-464. The binding pocket also includes regions of space near the “main” binding pocket that not occupied by atoms of PPARα but that are near the “main” binding pocket, and that are contiguous with the “main” binding pocket.

[0077] As used herein, the terms “PPAR gene” and “recombinant PPAR gene” mean a nucleic acid molecule comprising an open reading frame encoding a PPAR polypeptide of the present invention, including both exon and (optionally) intron sequences.

[0078] As used herein, the term “gene” is used for simplicity to refer to a functional protein, polypeptide or peptide encoding unit. As will be understood by those in the art, this functional term includes both genomic sequences and cDNA sequences. Preferred embodiments of genomic and cDNA sequences are disclosed herein.

[0079] As used herein, the term “DNA sequence encoding a PPAR polypeptide” can refer to one or more coding sequences within a particular individual. Moreover, certain differences in nucleotide sequences can exist between individual organisms, which are called alleles. It is possible that such allelic differences might or might not result in differences in amino acid sequence of the encoded polypeptide yet still encode a protein with the same biological activity. As is well known, genes for a particular polypeptide can exist in single or multiple copies within the genome of an individual. Such duplicate genes can be identical or can have certain modifications, including nucleotide substitutions, additions or deletions, all of which still code for polypeptides having substantially the same activity.

[0080] As used herein, the term “intron” means a DNA sequence present in a given gene that is not translated into protein.

[0081] As used herein, the term “interact” means detectable interactions between molecules, such as can be detected using, for example, a yeast two hybrid assay. The term “interact” is also meant to include “binding” interactions between molecules. Interactions can, for example, be protein-protein or protein-nucleic acid in nature.

[0082] As used herein, the terms “cells,” “host cells” or “recombinant host cells” are used interchangeably and mean not only to the particular subject cell, but also to the progeny or potential progeny of such a cell. Because certain modifications can occur in succeeding generations due to either mutation or environmental influences, such progeny might not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein.

[0083] As used herein, the term “agonist” means an agent that supplements or potentiates the bioactivity of a functional PPAR gene or protein or of a polypeptide encoded by a gene that is up- or down-regulated by a PPAR polypeptide and/or a polypeptide encoded by a gene that contains a PPAR binding site or response element in its promoter region.

[0084] As used herein, the term “antagonist” means an agent that decreases or inhibits the bioactivity of a functional PPAR gene or protein, or that supplements or potentiates the bioactivity of a naturally occurring or engineered non-functional PPAR gene or protein. Alternatively, an antagonist can decrease or inhibit the bioactivity of a functional gene or polypeptide encoded by a gene that is up- or down-regulated by a PPAR polypeptide and/or contains a PPAR binding site or response element in its promoter region. An antagonist can also supplement or potentiate the bioactivity of a naturally occurring or engineered non-functional gene or polypeptide encoded by a gene that is up- or down-regulated by a PPAR polypeptide, and/or contains a PPAR binding site or response element in its promoter region.

[0085] As used herein, the terms “chimeric protein” or “fusion protein” are used interchangeably and mean a fusion of a first amino acid sequence encoding a PPAR polypeptide with a second amino acid sequence defining a polypeptide domain foreign to, and not homologous with, any domain of a PPAR polypeptide. A chimeric protein can include a foreign domain that is found in an organism that also expresses the first protein, or it can be an “interspecies” or “intergenic” fusion of protein structures expressed by different kinds of organisms. In general, a fusion protein can be represented by the general formula X-PPAR-Y, wherein PPAR represents a portion of the protein which is derived from a PPAR polypeptide, and X and Y are independently absent or represent amino acid sequences which are not related to a PPAR sequence in an organism, which includes naturally occurring mutants.

II. Description of Tables

[0086] Table 1 is a table summarizing the crystal and data statistics obtained from the crystallized ligand binding domain of PPARα. Data on the unit cell are presented, including data on the crystal space group, unit cell dimensions, molecules per asymmetric cell and crystal resolution.

[0087] Table 2 is a table of the atomic structure coordinate data obtained from X-ray diffraction from the ligand binding domain of PPARα in complex with a ligand.

[0088] Table 3 is a table of the atomic structure coordinate data obtained from X-ray diffraction from the ligand binding domain (residues 207-441) of a PPARδ crystal (Xu et al., (1999) Mol. Cell 3: 397-403, PDB ID: 1GWX; Genbank Accession No. L07592; available online at http://www.rcsb.org/pdb/). The coordinate data from the PPARδ ligand binding domain were used in the molecular replacement solution of the PPARα ligand binding domain crystal form.

[0089] Table 4 is a sequence alignment which shows sequence similarities between the PPARα, PPARγ and PPARδ sequences. The binding site residues are denoted by small boxes and represent those residues lying within 5.0 angstroms of the ligand.

III. General Considerations

[0090] The present invention will usually be applicable mutatis mutandis to all PPARs, as discussed herein based, in part, on the patterns of PPAR structure and modulation that have emerged as a consequence of determining the three dimensional structure of PPARα with bound ligand. Analysis and alignment of amino acid sequences, and X-ray and NMR structure determinations, have shown that nuclear receptors have a modular architecture with three main domains:

[0091] 1) a variable amino-terminal domain;

[0092] 2) a highly conserved DNA-binding domain (DBD); and

[0093] 3) a less conserved carboxy-terminal ligand binding domain (LBD).

[0094] In addition, nuclear receptors may have linker segments of variable length between these major domains. Sequence analysis and X-ray crystallography, including the work of the present invention, have confirmed that PPARs also have the same general modular architecture, with the same three domains. The function of the PPARs in human cells presumably requires all three domains in a single amino acid sequence. However, the modularity of the PPARs permits different domains of each protein to separately accomplish certain functions. Some of the functions of a domain within the full-length receptor are preserved when that particular domain is isolated from the remainder of the protein. Using conventional protein chemistry techniques, a modular domain can sometimes be separated from the parent protein. Using conventional molecular biology techniques, each domain can usually be separately expressed with its original function intact or, as discussed herein below, chimeras comprising two different proteins can be constructed, wherein the chimeras retain the properties of the individual functional domains of the respective nuclear receptors from which the chimeras were generated.

[0095] The amino terminal domain of the PPAR subtypes is the least conserved of the three domains. This domain is involved in transcriptional activation and, in some cases, its uniqueness may dictate selective receptor-DNA binding and activation of target genes by PPAR subtypes. This domain can display synergistic and antagonistic interactions with the domains of the LBD.

[0096] The DNA binding domain has the most highly conserved amino acid sequence amongst the PPARs. It typically contains about 70 amino acids that fold into two zinc finger motifs, wherein a zinc atom coordinates four cysteines. The DBD contains two perpendicularly oriented α-helixes that extend from the base of the first and second zinc fingers. The two zinc fingers function in concert along with non-zinc finger residues to direct the PPAR to specific target sites on DNA and to align receptor heterodimer interfaces. Various amino acids in the DBD influence spacing between two half-sites (which usually comprises six nucleotides) for receptor heterodimerization. The optimal spacings facilitate cooperative interactions between DBDs, and D box residues are part of the dimerization interface. Other regions of the DBD facilitate DNA-protein and protein-protein interactions required for RXR-PPAR heterodimerization.

[0097] The LBD is the second most highly conserved domain in these receptors. As its name suggest, the LBD binds ligands. With many nuclear receptors, including the PPARs, binding of the ligand can induce a conformational change in the LBD that can, in turn, activate transcription of certain target genes. The LBD also participates in other functions, including dimerization and nuclear translocation.

[0098] X-ray structures have shown that most nuclear receptor LBDs adopt the same general folding pattern. This fold consists of 10-12 alpha-helices arranged in a bundle, together with several beta-strands, additional alpha-helices and linking segments. The major alpha helices and beta-strands have been numbered differently in different publications. This patent will follow the numbering scheme of Nolte et al., (Nolte et al., (1998) Nature 395:137-43), where the major alpha-helices and beta-strands are designated sequentially through the amino acid sequence as H1, H2, S1, H2′, H3, H3′, H4, H5, S2, S3, S4, H6, H7, H8, H9, H10 and HAF. The alpha-helix at the C-terminal end, HAF, is also called “helix-AF”, “helix-AF2” or the “AF2 helix”. Structural studies have shown that most of the alpha-helices and beta-strands have the same general position and orientation in all nuclear receptor structures, whether ligand is bound or not. However, the AF2 helix has been found in different positions and orientations relative to the main bundle, depending on the presence or absence of the ligand, and also on the chemical nature of the ligand. These structural studies have suggested that many nuclear receptors share a common mechanism of activation, where binding of activating ligands helps to stabilize the AF2 helix in a position and orientation adjacent to helices-3, -4, and -10, covering an opening to the ligand binding site. This position and orientation of the AF2 helix, which will be called the “active conformation”, creates a binding site for coactivators. See, e.g., Nolte et al., (1998) Nature 395:137-43; Shiau et al., (1 998) Cell 95: 927-37. This coactivator binding site has a central lipophilic pocket that can accommodate feucine side-chains from coactivators, as well as a “charge-clamp” structure consisting primarily of a lysine residue from helix-3 and a glutamic acid residue from the AF2 helix. Structural studies have shown that coactivator peptides containing the sequence LXXLL (where L is leucine and X can be a different amino acid in different cases) can bind to this coactivator binding site by making interactions with the charge clamp lysine and glutamic acid residues, as well as the central lipophilic region. This coactivator binding site is disrupted when the AF2 helix is shifted into other positions and orientations. In PPAR-γ, activating ligands such as rosiglitazone (BRL49653) make a hydrogen bonding interaction with tyrosine-473 in the AF2 helix. Nolte et al., (1998) Nature 395:137-43; Gampe et al., (2000) Mol. Cell 5: 545-55. This interaction is believed to stabilize the AF2 helix in the active conformation, thereby allowing coactivators to bind and thus activating transcription from target genes. With certain antagonist ligands, or in the absence of any ligand, the AF2 helix may be held less tightly in the active conformation, or may be free to adopt other conformations. This would either destabilize or disrupt the coactivator binding site, thereby reducing or eliminating coactivator binding and transcription from certain target genes. Some of the functions of the PPAR protein depend on having the full-length amino acid sequence and certain partner molecules, such as coactivators and DNA. However, other functions, including ligand binding and ligand-dependent conformational changes, may be observed experimentally using isolated domains, chimeras and mutant molecules.

[0099] As described herein, the LBD of a PPAR can be expressed, crystallized, its three dimensional structure determined with a ligand bound as disclosed in the present invention, and computational methods can be used to design ligands to its LBD.

IV. Synthesis of Compound 1 and Intermediates

[0100] Compound 1, which was co-crystallized with the PPARα LBD in the present invention, can be conveniently prepared by a general process wherein a moiety like (A) is coupled to an acid (B) using a peptide coupling reaction or by alkylation of (A) using a suitable non nucleophilic amine with an acid chloride (C). Preferably, R is 1-6 alkyl, which can be hydrolyzed off or, is readily hydrolyzable.

[0101] A preferred synthesis of (A) when X1 is O and X2 is NH (and R1 and R2 are H) is:

[0102] Note that this synthesis is preferably carried out with the amine where the alcohol function is already alkylated with the acid side chain protected by R. For example, when n is 1, X1 is O, X2 is NH, Y is S, Z is N, R1 and R2 are H, and R3 is 4-F3C-phenyl:

[0103] Some of the intermediates of type A are commercially available while others can be synthesized by techniques apparent to a person skilled in the art. The synthesis of intermediates of type B is illustrated below.

[0104] Compound 1 can be made by an alternative method in which compounds of formula (D) are reacted with ethyl 2-bromo-2 methyl propionate to produce an ethyl ester, which may be hydrolyzed to produce the free acid.

[0105] Compounds of formula (D) may be prepared from the reaction between compounds of formula (B) and compounds of formula (E) with HOBT/EDC/NEt3 when X2 is NH or NCH3 or DIC/DMAP/NEt3 when X2 is O.

[0106] The invention is further illustrated by the following examples which should not be construed as constituting a limitation thereto.

[0107] IV.A. Synthesis of Intermediate 1

[0108] Formation of Intermediate 1 follows the procedure described by Stout (Stout, (1983) J. Med. Chem. 26(6): 808-13). To 4-methoxybenzyl amine (25 g, 0.18 mol; Aldrich) is added 46% HBr in H2O (106 ml, 0.9 mol; Aldrich). The reaction is refluxed overnight, then the reaction is cooled to 0° C. and neutralized to pH7 slowly with KOH(s). The reaction is allowed to stir for ˜30 min, then the solid filtered and dried. The solid is redisolved in hot MeOH, filtered and the solution cooled to afford 19 g (85%) intermediate 1.

[0109] IV.B. Synthesis of Intermediate 2

[0110] A solution of ethyl 2-chloroacetoacetate (35.3 g, 29.7 mL, 0.21 mol) and 4-(trifluoromethyl)thiobenzamide (44 g, 0.21 mol) in EtOH (300 mL) is refluxed overnight. After cooling to room temperature the solvent is removed in vacuo. The final product (Intermediate 2) is recrystallized from a minimum of MeOH to afford 40 g (59%) of final product as a white solid.

[0111] IV.C. Synthesis of Intermediate 3

[0112] To Intermediate 2 (1.84 g, 5.8 mmol) in THF is added 1N LiOH (6 mL, 6 mmol) and the reaction stirred at room temperature. After ˜3 h, the reaction is neutralized with 1N HCl, extracted 3×100 mL EtOAc, dried over Na2SO4, filtered and the solvent removed under vaccum to afford 1.5 g (89%) of Intermediate 3 as a white solid.

[0113] IV.D. Synthesis of Intermediate 4

[0114] To intermediate 3 (1 g, 7 mmol) in CH2Cl2/DMF (1:1) is added HOBT (565 mg, 4.2 mmol; Aldrich), EDC (800 mg, 4.2 mmol; Aldrich) and Intermediate 1 (860 mg, 7 mmol). The reaction is stirred at room temperature for 18 h. The solvent is then removed in vacuo, treated with H2O and extracted 3×100 mL CH2Cl2. The organic phases are then combined and washed with 1N HCl, dried over Na2SO4, filtered and evaporated to afford a mixture (N-substituted and N,O-substituted). The mixture is disolved in MeOH and treated with 1N NaOH. The reaction is stirred 18 h at 50° C. The solvent removed in vacuo, dissolved in CH2Cl2, washed with H2O, and dried over Na2SO4. The solvent evaporated the residue chromatographed (CH2Cl2/MeOH: 99/1) to afford 610 mg (47%) of Intermediate 4 as a white solid.

[0115] IV.E. Synthesis of Intermediate 5

[0116] 2-methyl-2-[4-{[(4-methyl-2-[4-trifluoromethylphenyl]thiazol-5 ylcarbonyl)amino]methyl}phenoxy]propionic acid ethyl ester

[0117] To Intermediate 4 (710 mg, 1.81 mmol) in DMF (50 mL) is added the K2CO3 (275 mg, 1.99 mmol) followed by the ethyl 2-bromo-2-methylpropanate (280 μL, 1.91 mmol; Aldrich) and the reaction is heated to 80° C. After 18 h, the reaction is cooled to room temperature and the solvent removed in vacuo. The residue is treated with water (200 mL), extracted 3×50 mL CH2Cl2, dried over Na2SO4, filtered and the solvent removed under vaccum to afford 680 mg (77%) of Intermediate 5 as a clear oil.

[0118] IV.F. Synthesis of Compound 1

[0119] 2-methyl-2-[4-{[(4-methyl-2-[4-trifluoromethylphenyl]-thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid

[0120] To Intermediate 5 (680 mg, 1.39 mmol) in MeOH is added 1N NaOH (1.6 mL, 1.6 mmol) and the reaction is stirred at 60° C. After 18 h, the reaction is cooled to room temperature and the solvent evaporated. The residue treated with 1N HCl, extracted 3×20 mL THF and the solvent is removed under vacuum to afford 500 mg (75%) of Compound 1.

[0121] V. Production of PPAR Polypeptides

[0122] The native and mutated PPAR polypeptides, and fragments thereof, of the present invention can be chemically synthesized in whole or part using techniques that are well-known in the art (See, e.g., Creighton, (1983) Proteins: Structures and Molecular Principles, W.H. Freeman & Co., New York, incorporated herein in its entirety). Alternatively, methods which are well known to those skilled in the art can be used to construct expression vectors containing a partial or the entire native or mutated PPAR polypeptide coding sequence and appropriate transcriptional/translational control signals. These methods include in vitro recombinant DNA techniques, synthetic techniques and in vivo recombination/genetic recombination. See, for example, the techniques described throughout Sambrook et al., (1989) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York, and Ausubel et al., (1989) Current Protocols in Molecular Biology, Greene Publishing Associates and Wiley Interscience, New York, both incorporated herein in their entirety.

[0123] A variety of host-expression vector systems can be utilized to express a PPAR coding sequence. These include but are not limited to microorganisms such as bacteria transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing a PPAR coding sequence; yeast transformed with recombinant yeast expression vectors containing a PPAR coding sequence; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing a PPAR coding sequence; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing a PPAR coding sequence; or animal cell systems. The expression elements of these systems vary in their strength and specificities.

[0124] Depending on the host/vector system utilized, any of a number of suitable transcription and translation elements, including constitutive and inducible promoters, can be used in the expression vector. For example, when cloning in bacterial systems, inducible promoters such as pL of bacteriophage λ, plac, ptrp, ptac (ptrp-lac hybrid promoter) and the like can be used. When cloning in insect cell systems, promoters such as the baculovirus polyhedrin promoter can be used. When cloning in plant cell systems, promoters derived from the genome of plant cells, such as heat shock promoters; the promoter for the small subunit of RUBISCO; the promoter for the chlorophyll a/b binding protein) or from plant viruses (e.g., the 35S RNA promoter of CaMV; the coat protein promoter of TMV) can be used. When cloning in mammalian cell systems, promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5K promoter) can be used. When generating cell lines that contain multiple copies of the tyrosine kinase domain DNA, SV40-, BPV- and EBV-based vectors can be used with an appropriate selectable marker.

[0125] VI. Formation of PPARα Ligand Binding Domain Crystals

[0126] In one embodiment, the present invention provides crystals of PPARα LBD. The crystals were obtained using the methodology disclosed in the Examples. The PPARα LBD crystals, which can be native crystals, derivative crystals or co-crystals, have orthorhombic unit cells (an orthorhombic unit cell is a unit cell wherein a≠b≠c, and wherein α=β=γ=90°) and space group symmetry P21212. There is one PPARα LBD molecule in the asymmetric unit. In this PPARα crystalline form, the unit cell has dimensions of a=61.3 Å, b=103.5 Å, c=49.9 Å, and α=β=γ=90°. This crystal form can be formed in a crystallization reservoir comprising 4-8% PEG 3350, 100-200 mM NaF, and 12-16% 2,5 hexanediol.

[0127] In another PPARα crystal form, the unit cell has dimensions of a=95.58 Å, b=122.06 Å, c=122.10 Å, α=β=γ=90° and belongs to the space group P212121. There are four PPARα LBD molecules in the asymmetric unit of this crystal form. This crystal form can be formed in a crystallization reservoir comprising 50 mM bis-tris-propane, 4-6% PEG 3350, 150 mM NaNO3, 16% 2,5 hexanediol, and 1-3 mM YCl3.

[0128] VI.A. Preparation of PPAR Crystals

[0129] The native and derivative co-crystals, and fragments thereof, disclosed in the present invention can be obtained by a variety of techniques, including batch, liquid bridge, dialysis, vapor diffusion and hanging drop methods (See, eg., McPherson, (1982) Preparation and Analysis of Protein Crystals, John Wiley, New York.; McPherson, (1990) Eur. J. Biochem. 189:1-23.; Weber, (1991) Adv. Protein Chem. 41:1-36). In a preferred embodiment, the vapor diffusion and hanging drop methods are used for the crystallization of PPAR polypeptides and fragments thereof.

[0130] In general, native crystals of the present invention are grown by dissolving substantially pure PPAR polypeptide or a fragment thereof in an aqueous buffer containing a precipitant at a concentration just below that necessary to precipitate the protein. Water is removed by controlled evaporation to produce precipitating conditions, which are maintained until crystal growth ceases.

[0131] In a preferred embodiment of the invention, native crystals are grown by vapor diffusion (See, e.g., McPherson, (1982) Preparation and Analysis of Protein Crystals, John Wiley, New York.; McPherson, (1990) Eur. J. Biochem. 189:1-23). In this method, the polypeptide/precipitant solution is allowed to equilibrate in a closed container with a larger aqueous reservoir having a precipitant concentration optimal for producing crystals. Generally, less than about 25 μL of PPAR polypeptide solution is mixed with an equal volume of reservoir solution, giving a precipitant concentration about half that required for crystallization. This solution is suspended as a droplet underneath a coverslip, which is sealed onto the top of the reservoir. The sealed container is allowed to stand, until crystals grow. Crystals generally form within two to six weeks, and are suitable for data collection within approximately seven to ten weeks. Of course, those of skill in the art will recognize that the above-described crystallization procedures and conditions can be varied.

[0132] VI.B. Preparation of Derivative Crystals

[0133] Derivative crystals of the present invention, e.g. heavy atom derivative crystals, can be obtained by soaking native crystals in mother liquor containing salts of heavy metal atoms. Such derivative crystals are useful for phase analysis in the solution of crystals of the present invention. In a preferred embodiment of the present invention, for example, soaking a native crystal in a solution containing methyl-mercury chloride provides derivative crystals suitable for use as isomorphous replacements in determining the X-ray crystal structure of a PPAR polypeptide. Additional reagents useful for the preparation of the derivative crystals of the present invention will be apparent to those of skill in the art after review of the disclosure of the present invention presented herein.

[0134] VI.C. Preparation of Co-crystals

[0135] Co-crystals of the present invention can be obtained by soaking a native crystal in mother liquor containing compounds known or predicted to bind the LBD of a PPAR, or a fragment thereof. Alternatively, co-crystals can be obtained by co-crystallizing a PPAR LBD polypeptide or a fragment thereof in the presence of one or more compounds known or predicted to bind the polypeptide. In a preferred embodiment, such a compound is Compound 1.

[0136] VI.D. Solving a Crystal Structure of the Present Invention

[0137] Crystal structures of the present invention can be solved using a variety of techniques including, but not limited to, isomorphous replacement, anomalous scattering or molecular replacement methods. Computer software packages will also be helpful in solving a crystal structure of the present invention. Applicable software packages include but are not limited to X-PLOR™ program (Brünger, (1992) X-PLOR, Version 3.1. A System for X-ray Crystallography and NMR, Yale University Press, New Haven, Conn.; X-PLOR is available from Molecular Simulations, Inc., San Diego, Calif.), Xtal View (McRee, (1992) J. Mol. Graphics 10: 44-47; X-tal View is available from the San Diego Supercomputer Center). SHELXS 97 (Sheldrick (1990) Acta Cryst. A46: 467; SHELX 97 is available from the Institute of Inorganic Chemistry, Georg-August-Universität, Göttingen, Germany), HEAVY (Terwilliger, Los Alamos National Laboratory) and SHAKE-AND-BAKE (Hauptman, (1997) Curr. Opin. Struct. Biol. 7: 672-80; Weeks et al., (1993) Acta Cryst. D49: 179; available from the Hauptman-Woodward Medical Research Institute, Buffalo, N.Y.) can be used. See also, Ducruix & Geige, (1992) Crystallization of Nucleic Acids and Proteins: A Practical Approach, IRL Press, Oxford, England, and references cited therein.

[0138] VII. Characterization and Solution of a PPARα Ligand Binding Domain Crystal

[0139] VII.A Unique Structural Differences Between PPARα and Other PPARs

[0140] The PPARα LBD-ligand structure was solved here using molecular replacement techniques. The overall folding of the protein backbone, and the binding mode of Compound 1, are shown in the ribbon diagram of FIG. 1. Specific interactions between Compound 1 and the protein are shown schematically in FIG. 2. The structure of the PPARγ LBD was solved previously in the apo form, i.e., with no ligand, and also with a thiazolidinedione ligand (rosiglitazone) and a coactivator peptide (Nolte et al., (1998) Nature 395:137-43). The apo structure has also been determined independently (Uppenberg et al., (1998) J. Biol. Chem. 273: 31108-12). In addition, the structure of the PPARγ LBD has been determined with a partial agonist, GW0072 (Oberfield et al., (1999) Proc. Nat. Acad. Sci. 96: 6102-106). The structure of the PPARγ LBD has also been determined in the heterodimeric complex with RXRα, together with coactivator peptides, with rosiglitazone, and also with a carboxylic acid ligand, GI262570 (Gampe et al., (2000) Mol. Cell 5: 545-55). The structure of the PPARδ LBD has been determined in the apo form, and with eicosapentaenoic acid, and with the synthetic compound GW2433 (Xu et al., (1999) Mol. Cell 3: 397-403).

[0141] To facilitate comparison, the structures were first translated and rotated into a common position and orientation as shown in FIG. 1. This superimposition operation was done with the MVP program (Lambert, (1997) in Practical Application of Computer-Aided Drug Design, (Charifson, ed.), pp. 243-303, Marcel-Dekker, New York) by first aligning the amino acid sequences to identify corresponding residues in the three different PPARs, and then rotating and translating so as to superimpose corresponding C60 or backbone atoms from the aligned residues. With this translation and rotation, most of the major alpha-helices and beta-strands of the three PPARs are closely superimposed. The AF2 helix is well superimposed in most of the structures, but is shifted into a different position in certain subunits of structures of PPARγ either in the absence of ligand (apo), or in the presence of the partial agonist GW0072. This shift provides evidence that the PPAR AF2 helix can shift out of the active conformation, and that it is more likely to do so in the absence of a strongly activating ligand. In the above listed PPAR X-ray structures, the ligands that act as strong agonists (rosiglitazone, GI262570, eicosapentaenoic acid, GW2433, Compound 1) are all oriented with the acid group near the AF2 helix, and they all make a hydrogen bond with a tyrosine residue in the AF2 helix (Tyr464 in PPARα, Tyr473 in PPARγ, Tyr437 in PPARδ). The partial agonist, GW0072, also has a carboxyl group, but it is oriented differently, and fails to make any hydrogen bond with the AF2 tyrosine. This suggests that the hydrogen bond between the ligand and the AF2 tyrosine helps to hold the AF2 helix in the active conformation and thereby facilitate coactivator binding. See, Xu et al., (1999) Mol. Cell 3: 397-403 and Oberfield et al., (1999) Proc. Nat Acad. Sci. 96: 6102-106.

[0142] To facilitate discussion, it is useful to establish a nomenclature for regions of the ligand and the ligand binding pocket. The strongly activating ligands in these X-ray structures all have an acid group that binds near the AF2 tyrosine, and a lipophilic “tail” that extends into a lipophilic pocket. The acid group can be called the acid “headgroup”, and the site near the AF2 helix into which it binds can be called the “headgroup binding site”. In rosiglitazone, GI262570 and Compound 1, the lipophilic tail is directed into a lipophilic pocket delineated by helix-2′, helix-3 and the beta sheet. This will be called the “lower tail pocket” or “lower pocket”. In the structure of PPARδ bound to eicosapentaenoic acid, the eicosapentaenoic acid was found in two different binding modes with roughly equal occupancy (Xu et al., (1999) Mol. Cell 3: 397-403). In both binding modes, the acid headgroup bound in the headgroup binding site near Tyr 437. In one binding mode, the lipophilic tail was directed into the lower tail pocket. However, in the other binding mode, the lipophilic tail was directed into a different pocket, delineated by helix-3, helix-5, the beta sheet and the loop between helix-1 and helix-2. This will be called the “upper tail pocket.” GW2433 has a branched tail, and was found to bind with one branch in the lower pocket, and with the other branch in the upper pocket (Xu et al., (1999) Mol. Cell 3: 397-403). GI262570 has an additional lipophilic benzophenone group near the acid headgroup. This benzophenone group was found to be directed into a lipophilic pocket delineated by helix-3, helix-7, helix-10 and the loop between helix-10 and the AF2 helix. This will be subsequently referred to as the “benzophenone pocket.”

[0143] Comparing the backbone structures, there are substantial differences between PPARα, PPARγ and PPARδ in the “loop” region between helix-2 and strand-1, the loop region between helix-2′ and helix-3, and the loop region between helix-10 and the AF2 helix. There are also smaller differences in the loop region between helix-1 and helix-2, and the loop region between helix-6 and helix-7. Helices 2, 2′ and 3′ are closely superimposed, but have slightly different lengths, as indicated in Table 4. Helix-10 has the same length in all structures, but bends differently over the ligand binding pocket in PPARα, PPARγ and PPARδ. Some of these structural differences are visible in FIG. 3. Many of these structural differences lie close to the ligand binding pocket, and could therefore be important in the receptor selectivity of different ligands.

[0144] Helix-2′ and the loop between helix-2′ and helix-3 (the 2′-3 loop) together serve as one wall for the “lower tail pocket” in all three PPARs. Helix-2′, and the 2′-3 loop, adopt different conformations in some of the different PPARγ structures. In particular, helix-2′ is shorter in the homodimer structures of PPARγ bound to rosiglitazone and GW0072, and in the absence of ligand, than it is in the RXRα/PPARγ heterodimer structures where PPARγ is bound to rosiglitazone or GI262570. Some of these conformational differences might result from differences in crystal packing. However, the RXRα/PPARγ heterodimer represents the closer approximation to the biologically active complex, and will be used here to represent the most relevant conformation of PPARγ. By contrast, helix-2′ and the 2′-3 loop adopt more nearly equivalent backbone conformations in the available X-ray structures of PPARα and PPARδ. Considering the conformation in the RXRα/PPARγ/GI262570 heterodimer structure, helix-2′ is longer in PPARα and PPARδ, and the C-terminal end of the helix adopts different conformations in the three PPARs. In PPARα, the last residue of the helix, Leu254, makes the expected alpha-helical hydrogen bonds, but bulges away from the axis of the helix towards the ligand. This bulged conformation allows Leu254 and Val255 to cover the “bottom” of the lower tail pocket, effectively narrowing the mouth of the pocket. In PPARδ, the C-terminal end of helix-2′ is wound more loosely, such that the corresponding residue, Leu226, cannot cover the bottom of the ligand binding pocket. Instead, the 2′-3 loop adopts a different conformation that places the side-chain of Trp228 in the bottom of the lower tail pocket. This shortens the lower tail pocket slightly, and also constricts the opening to solvent. In PPARγ, helix-2′ is bent such that its corresponding residue, Ile262, is shifted farther from the pocket. Also, the next two residues, Lys263 and Phe264, adopt the helical conformation, effectively extending helix-2 by two residues, such that Lys263 is far from the ligand and cannot cover the solvent channel. This leaves a very wide opening to solvent at this position in PPARγ, as depicted by the large, wide cavity region above the 2′-3 loop in FIG. 5. The opening is much narrower in PPARα and PPARδ, as depicted in FIGS. 4 and 6. These variations in the backbone conformation would be difficult or impossible to predict from the previously available X-ray structures with any homology modeling procedure. Nonetheless, very accurate models for helix-2′ and the 2′-3 loop in all three PPARs would be essential for understanding the binding mode and receptor selectivity of ligands that occupy the lower tail pocket.

[0145] The loop between helix-1 and helix-2 (the “1-2 loop”) serves as a wall at the far end of the upper tail pocket. Residues in this 1-2 loop come close to the tail of eicosapentaenoic acid (in its upper tail pocket binding mode), and close to the fluoro-,chloro-phenyl ring of GW2433 in PPARδ. Several backbone amide CO and NH groups are directed towards the ligand binding site, and could serve as hydrogen bonding partners with an appropriately designed ligand. However, the backbone conformation in the 1-2 loop is slightly different in PPARα, PPARγ and PPARδ. In particular, the backbone amide CO and NH groups have slightly different orientations in PPARα, PPARγ and PPARδ. Some of these differences may result from the presence of a proline at position 227 in PPARγ, whereas PPARα and PPARδ have asparagines at this position. These subtle differences would be difficult or impossible to predict to high accuracy using the previously available X-ray structures with standard homology modeling procedures. Nonetheless, a very accurate model of this loop conformation would be essential for understanding the receptor selectivity of ligands that interact with this loop.

[0146] The C-terminal end of helix-10 and the loop between helix-10 and the AF2 helix (the “10-AF2 loop”) together serve as one wall for the headgroup binding site and the benzophenone pocket. An additional wall is provided by a glutamine residue in helix-3 (Gln277 in PPARα, Gln286 in PPARγ, Gln250 in PPARδ) that reaches across the benzophenone binding site to make hydrogen bonds with backbone CO and NH groups from the 10-AF2 loop. This glutamine side-chain, and the 10-AF2 loop itself, adopt different conformations in the three PPARs. In PPARα and PPARδ, the glutamine side-chain adopts conformations that narrow the benzophenone pocket substantially. In addition, in PPARα and PPARδ, the 10-AF2 loop adopts a conformation that crowds a phenylalanine from helix-3 (Phe273 in PPARα, Phe282 in PPARγ, Phe246 in PPARδ) more in PPARα and PPARδ than in PPARγ. These two structural differences cause a slight narrowing of the benzophenone pocket in PPARα, and a more substantial narrowing in PPARδ. This can be seen by comparison of PPARα and PPARδ in FIGS. 4 and 6 with PPARγ in FIG. 5. The narrowing is sufficient to significantly reduce the binding affinity of ligands that have a benzophenone group at this position. The narrowing in PPARα and PPARδ suggests that smaller groups should be used at this position to obtain good binding to PPARα, and substantially smaller groups should be used to obtain good binding to PPARδ. Aside from these changes that narrow the pocket in PPARα and PPARδ, there are also structural changes that modulate the shape of the pocket and the position and orientation of potential hydrogen bonding groups. For example, the C-terminal end of helix-10 bends inwards toward the ligand binding site in all three PPARs. However, the bend is slightly different in the different PPARs, placing corresponding side-chains in slightly different positions. These variations in the backbone conformation, and corresponding changes in side-chain conformation, would be difficult or impossible to predict from the previously available X-ray structures with any available homology modeling procedure. Nonetheless, very accurate models for helix-10, the 10-AF2 loop and the side-chains in this region would be essential for understanding the binding mode and receptor selectivity of ligands that occupy the benzophenone pocket.

[0147] Aside from these unexpected differences in the backbone structure of PPARα, the present X-ray structure also revealed differences involving side-chains. In some cases, these differences involve residue positions where the amino acid is different in PPARα from that in either PPARγ or PPARδ or both. In other cases, PPARα may have the same amino acid at a particular residue position as PPARγ or PPARδ or both, but the amino acid side-chain adopts a different conformation in PPARα.

[0148] One of the most important side-chain differences is Tyr314 in PPARα, a position that corresponds to His323 in PPARγ and His287 in PPARδ. In PPARγ and PPARδ, this histidine residue makes a hydrogen bond with the acidic headgroup of the ligand for all strongly activating ligands for which structures are available. The present PPARα structures shows that Tyr314 also makes a hydrogen bond with the acidic headgroup of Compound 1. However, the tyrosine OH lies farther from the protein backbone than the corresponding hydrogen bonding atoms in histidine. Consequently, changing histidine to tyrosine could potentially require a change in the position and/or orientation and/or conformation of the ligand, or changes in the conformation of the PPARα protein. The present PPARα crystal structure showed that the protein backbone is essentially unchanged in this region of PPARα, compared with PPARγ and PPARδ. Instead, the acid headgroup of the ligand is shifted and rotated in such a way that it can still make hydrogen bonds with Ser280, Tyr314, His440 and Tyr464. This involves small changes in the conformations of Tyr314, His440 and Tyr464, relative to PPARγ and PPARδ. Also, this involves a larger change in the conformation of Ser280, which unexpectedly adopts a conformation different from that of Ser289 in PPARγ bound to GI262570. The PPARα conformation places the Ser280 side-chain oxygen near the position of the side-chain oxygen of Thr253 in PPARδ bound to GW2433. The exact shift and rotation, and the exact conformations of the side-chains of Ser280, Tyr314, His440 and Tyr464, would be difficult or impossible to predict without this X-ray crystal structure of PPARα. However, this shift and rotation do significantly affect the position of the whole ligand within the ligand binding site. The position and orientation of the ligand carboxylate group revealed in this PPARα X-ray structure, and the interactions it makes with Ser280, Tyr314, His440 and Tyr464, can serve as a template for docking other compounds into PPARα using molecular modeling procedures.

[0149] This PPARα X-ray structure also revealed numerous other side-chains where the conformation in PPARα was different from that in PPARγ and/or PPARδ, and where the diffidence could affect the shape of the ligand binding pocket, and the position, orientation and/or conformation of the ligand. These additional residues with differences include, but are not limited to, Gln277, Phe273, His274, Ile354, Leu321, Met320, Met330 and Glu251. The side-chain chain conformational differences involving Gln277, Phe273 and Ile354 affect the volume and detailed shape of the headgroup binding site and/or the benzophenone pocket. His274 may affect these pockets indirectly, through its effect on Gln277 and Phe273. Leu321, Met320, Met330 and Glu251 affect the shape and volume of the upper and lower tail pockets. Numerous other side-chains also affect the size, shape and electrostatic character of the ligand binding site, and the position, orientation and conformation of the ligand within the ligand binding site. An understanding of the PPARα, PPARγ and PPARδ selectivity of various ligands would depend on having an accurate structure of each of the three PPARs, as well as an accurate position of the whole ligand within the pocket. This PPARα X-ray structure provides an accurate protein structure, as well as a template for modeling alternative ligands.

[0150] VII.B Characterization of the PPARα Binding Pocket

[0151] The ligand binding domain of PPARα was co-crystallized with Compound 1, which has the IUPAC name 2-methyl-2-[4-{[(4-methyl-2-[4-trifluoromethylphenyl] thiazol-5-yl-carbonyl) amino] methyl} phenoxy] propionic acid.

[0152] Compound 1 is an agonist of hPPARα and is useful for treatment of hPPARα mediated diseases or conditions including dyslipidemia, syndrome X, heart failure, hypercholesteremia, cardiovascular disease, type II diabetes mellitus, type I diabetes, insulin resistance, hyperlipidemia, obesity, inflammation, anorexia bulimia and anorexia nervosa.

[0153]
FIGS. 1, 2 and 7 depict the conformation and orientation of the ligand Compound 1 in the binding site. FIG. 1 depicts the overall orientation of the α helices and β strands of the ligand binding domain of PPARα as it binds Compound 1. Compound 1 is presented as a spacefilling model.

[0154] A more specific graphical description of the residues of the PPARα LBD involved in ligand binding is presented in FIG. 2. FIG. 2 is a schematic diagram depicting those residues of the PPARα LBD that interact with Compound 1 as it is bound in the binding pocket of the PPARα LBD. Note that FIG. 2 is a schematic diagram, and highlights residues that interact with the ligand and does not indicate intermolecular distances.

[0155] VII.C. Hydrogen Bonding in the Binding Pocket of the PPARα LBD

[0156] The hydrogen bonding scheme of the solvated binding pocket is presented in FIG. 7. In FIG. 7, atoms are shaded according to element, with carbon, fluorine, nitrogen, oxygen, sulfur and hydrogen in progressively lighter shades of gray. Sulfur is depicted with a slightly bigger ball, while hydrogen, fluorine and oxygen are depicted with slightly smaller balls. The hydrogen atoms shown here were not visible in the electron density, and were instead modeled into reasonable conformations (using standard bond lenghts and angles) to obtain possible hydrogen bond interactions, shown here with strings of small white balls. Each interaction is annotated with its distance in angstroms. Residues of the PPARα LBD binding pocket involved in hydrogen bonding are labeled. It is observed that hydrogen bonding relationships exist between the side chains of PPARα LBD residues and the ligand, between the side chains of PPARα LBD residues and solvent molecules, and between the ligand and solvent molecules. The hydrogen bonding pairs are identified by dotted lines.

[0157]
FIG. 7 highlights hydrogen bonding that occurs between solvent molecules (indicated as crosses in FIG. 7) and the side chains of PPARα LBD residues in the binding pocket. Residues that hydrogen bond to solvent and are visible in FIG. 7 include Ser-280, Ser-283, Thr-279 and Ala-333.

[0158] Additionally, FIG. 7 highlights those residues of the PPARα LBD that hydrogen bond directly to the ligand. Residues of the PPARα LBD in which side chains hydrogen bond directly to the ligand are visible in FIG. 7, and include His-440, Tyr-464, Tyr-314, Ser 280 and Thr-279.

[0159] VII.D. Generation of Easily-Solved PPAR Crystals

[0160] The present invention discloses a substantially pure PPAR LBD polypeptide in crystalline form. In a preferred embodiment, exemplified in the Figures and Laboratory Examples, PPARα is crystallized with bound ligand. Crystals are formed from PPAR LBD polypeptides that are usually expressed by a cell culture, such as E. coli. Bromo-, iodo- and substitutions can be included during the preparation of crystal forms and can act as heavy atom substitutions in PPAR ligands and crystals of PPARs. This method can be advantageous for the phasing of the crystal, which is a crucial, and sometimes limiting, step in solving the three-dimensional structure of a crystallized entity. Thus, the need for generating the heavy metal derivatives traditionally employed in crystallography can be eliminated. After the three-dimensional structure of a PPAR or PPAR LBD with or without a ligand bound is determined, the resultant three-dimensional structure can be used in computational methods to design synthetic ligands for PPARα and other PPAR polypeptides. Further activity structure relationships can be determined through routine testing, using assays disclosed herein and known in the art.

[0161] VIII. Uses of PPARα Crystals and the Three-Dimensional Structure of the Ligand Binding Domain of PPARα

[0162] VIII.A. Design and Development of PPAR Modulators

[0163] The knowledge of the structure of the PPARα ligand binding domain (LBD), an aspect of the present invention, provides a tool for investigating the mechanism of action of PPARα and other PPAR polypeptides in a subject. For example, various computer modelleing programs, as described herein, can predict the binding of various ligand molecules to the LBD of PPARα, PPARγ or PPARδ. Upon discovering that such binding in fact takes place, knowledge of the protein structure then allows design and synthesis of small molecules that mimic the functional binding of the ligand to the LBD of PPARα, and to the LBDs of other PPAR polypeptides. This is the method of “rational” drug design, further described herein.

[0164] Use of the isolated and purified PPARα crystalline structure of the present invention in rational drug design is thus provided in accordance with the present invention. Additional rational drug design techniques are described in U.S. Pat. Nos. 5,834,228 and 5,872,011, incorporated herein in their entirety.

[0165] Thus, in addition to the compounds described herein, other sterically similar compounds can be formulated to interact with the key structural regions of a PPAR in general, or of PPARα in particular. The generation of a structural functional equivalent can be achieved by the techniques of modeling and chemical design known to those of skill in the art and described herein. It will be understood that all such sterically similar constructs fall within the scope of the present invention.

[0166] VIII.A.1. Rational Drug Design

[0167] The three-dimensional structure of ligand-binding PPARα is unprecedented and will greatly aid in the development of new synthetic ligands for a PPAR polypeptide, such as PPAR agonists and antagonists, including those that bind exclusively to any one of the PPAR subtypes. In addition, the PPARs are well suited to modem methods, including three-dimensional structure elucidation and combinatorial chemistry, such as those disclosed in U.S. Pat. No. 5,463,564, incorporated herein by reference. Structure determination using X-ray crystallography is possible because of the solubility properties of the PPARs. Computer programs that use crystallography data when practicing the present invention will enable the rational design of ligands to these receptors. Programs such as RASMOL (Biomolecular Structures Group, Glaxo Wellcome Research & Development Stevenage, Hertfordshire, UK Version 2.6, August 1995, Version 2.6.4, December 1998, Copyright© Roger Sayle 1992-1999) can be used with the atomic structural coordinates from crystals generated by practicing the invention or used to practice the invention by generating three-dimensional models and/or determining the structures involved in ligand binding. Computer programs such as those sold under the registered trademark INSIGHT II® and such as GRASP (Nicholls et al., (1991) Proteins 11: 282) allow for further manipulations and the ability to introduce new structures. In addition, high throughput binding and bioactivity assays can be devised using purified recombinant protein and modern reporter gene transcription assays known to those of skill in the art in order to refine the activity of a designed ligand.

[0168] A method of identifying modulators of the activity of a PPAR polypeptide using rational drug design is thus provided in accordance with the present invention. The method comprises designing a potential modulator for a PPAR polypeptide of the present invention that will form non-covalent interactions with amino acids in the ligand binding pocket based upon the crystalline structure of the PPARα LBD polypeptide; synthesizing the modulator; and determining whether the potential modulator modulates the activity of the PPAR polypeptide. In a preferred embodiment, the modulator is designed for a PPARα polypeptide. Preferably, the PPARα polypeptide comprises the nucleic acid sequence of SEQ ID NO:1, and the PPARα LBD comprises the nucleic acid sequence SEQ ID NO:3. The determination of whether the modulator modulates the biological activity of a PPAR polypeptide is made in accordance with the screening methods disclosed herein, or by other screening methods known to those of skill in the art. Modulators can be synthesized using techniques known to those of ordinary skill in the art.

[0169] In an alternative embodiment, a method of designing a modulator of a PPAR polypeptide in accordance with the present invention is disclosed comprising: (a) selecting a candidate PPAR ligand; (b) determining which amino acid or amino acids of an PPAR polypeptide interact with the ligand using a three-dimensional model of a crystallized PPARα LBD; (c) identifying in a biological assay for PPAR activity a degree to which the ligand modulates the activity of the PPAR polypeptide; (d) selecting a chemical modification of the ligand wherein the interaction between the amino acids of the PPAR polypeptide and the ligand is predicted to be modulated by the chemical modification; (e) performing the chemical modification on the ligand to form a modified ligand; (f) contacting the modified ligand with the PPAR polypeptide; (g) identifying in a biological assay for PPAR activity a degree to which the modified ligand modulates the biological activity of the PPAR polypeptide; and (h) comparing the biological activity of the PPAR polypeptide in the presence of modified ligand with the biological activity of the PPAR polypeptide in the presence of the unmodified ligand, whereby a modulator of an PPAR polypeptide is designed.

[0170] VIII.A.2. Methods for Using the PPARα LBD Structural Coordinates For Molecular Design

[0171] For the first time, the present invention permits the use of molecular design techniques to design, select and synthesize chemical entities and compounds, including modulatory compounds, capable of binding to the ligand binding pocket or an accessory binding site of PPARα and the PPARα LBD, in whole or in part. Correspondingly, the present invention also provides for the application of similar techniques in the design of modulators of any PPAR polypeptide.

[0172] In accordance with a preferred embodiment of the present invention, the structure coordinates of a crystalline PPARα LBD can be used to design compounds that bind to a PPAR LBD (more preferably a PPARα LBD) and alter the properties of a PPAR LBD (for example, the dimerization or ligand binding ability) in different ways. One aspect of the present invention provides for the design of compounds that can compete with natural or engineered ligands of a PPAR polypeptide by binding to all, or a portion of, the binding sites on a PPAR LBD. The present invention also provides for the design of compounds that can bind to all, or a portion of, an accessory binding site on a PPAR that is already binding a ligand. Similarly, non-competitive agonists/ligands that bind to and modulate PPAR LBD activity, whether or not it is bound to another chemical entity, can be designed using the PPAR LBD structure coordinates of this invention.

[0173] A second design approach is to probe a PPAR or PPAR LBD (preferably a PPARα or PPARα LBD) crystal with molecules comprising a variety of different chemical entities to determine optimal sites for interaction between candidate PPAR or PPAR LBD modulators and the polypeptide. For example, high resolution X-ray diffraction data collected from crystals saturated with solvent allows the determination of the site where each type of solvent molecule adheres. Small molecules that bind tightly to those sites can then be designed and synthesized and tested for their PPARα modulator activity. Representative designs are also disclosed in published PCT application WO 99/26966.

[0174] Once a computationally-designed ligand is synthesized using the methods of the present invention or other methods known to those of skill in the art, assays can be used to establish its efficacy of the ligand as a modulator of PPAR (preferably PPARα) activity. After such assays, the ligands can be further refined by generating intact PPAR, or PPAR LBD, crystals with a ligand bound to the LBD. The structure of the ligand can then be further refined using the chemical modification methods described herein and known to those of skill in the art, in order to improve the modulation activity or the binding affinity of the ligand. This process can lead to second generation ligands with improved properties.

[0175] Ligands also can be selected that modulate PPAR responsive gene transcription by the method of altering the interaction of co-activators and co-repressors with their cognate PPAR. For example, agonistic ligands can be selected that block or dissociate a co-repressor from interacting with the PPAR, and/or that promote binding or association of a co-activator. Antagonistic ligands can be selected that block co-activator interaction and/or promote co-repressor interaction with a target receptor. Selection can be done via binding assays that screen for designed ligands having the desired modulatory properties. Preferably, interactions of a PPARα polypeptide are targeted. Suitable assays for screening that can be employed, mutatis mutandis in the present invention, are described in as described in Nichols et al., (1998) Anal. Biochem. 257: 112-19 and Xu et al., (1999) Mol. Cell 3: 397-403, which are incorporated herein in their entirety by reference.

[0176] VIII.A.3. Methods of Designing PPARα LBD Modulator Compounds

[0177] The design of candidate substances, also referred to as “compounds” or “candidate compounds”, that bind to or inhibit PPAR LBD-mediated activity according to the present invention generally involves consideration of two factors. First, the compound must be capable of physically and structurally associating with a PPAR LBD. Non-covalent molecular interactions important in the association of a PPAR LBD with its substrate include hydrogen bonding, van der Waals interactions and hydrophobic interactions.

[0178] Second, the compound must be able to assume a conformation that allows it to associate with a PPAR LBD. Although certain portions of the compound will not directly participate in this association with a PPAR LBD, those portions can still influence the overall conformation of the molecule. This, in turn, can have a significant impact on potency. Such conformational requirements include the overall three-dimensional structure and orientation of the chemical entity or compound in relation to all or a portion of the binding site, e.g., the ligand binding pocket or an accessory binding site of a PPAR LBD, or the spacing between functional groups of a compound comprising several chemical entities that directly interact with a PPAR LBD.

[0179] The potential modulatory or binding effect of a chemical compound on a PPAR LBD can be analyzed prior to its actual synthesis and testing by the use of computer modeling techniques that employ the coordinates of a crystalline PPARα LBD polypeptide of the present invention. If the theoretical structure of the given compound suggests insufficient interaction and association between it and a PPAR LBD, synthesis and testing of the compound is obviated. However, if computer modeling indicates a strong interaction, the molecule can then be synthesized and tested for its ability to bind and modulate the activity of a PPAR LBD. In this manner, synthesis of unproductive or inoperative compounds can be avoided.

[0180] A modulatory or other binding compound of a PPAR LBD polypeptide (preferably a PPARα LBD) can be computationally evaluated and designed via a series of steps in which chemical entities or fragments are screened and selected for their ability to associate with the individual binding sites or other areas of a crystalline PPARαLBD polypeptide of the present invention.

[0181] One of several methods can be used to screen chemical entities or fragments for their ability to associate with a PPAR LBD and, more particularly, with the individual binding sites of a PPAR LBD, such as ligand binding pocket or an accessory binding site. This process can begin by visual inspection of, for example, the ligand binding pocket on a computer screen based on the PPARα LBD atomic coordinates in Table 2. Selected fragments or chemical entities can then be positioned in a variety of orientations, or docked, within an individual binding site of a PPARα LBD as defined herein above. Docking can be accomplished using software programs such as those available under the tradenames QUANTA™ (Molecular Simulations Inc., San Diego, Calif.) and SYBYL™ (Tripos, Inc., St. Louis, Miss.), followed by energy minimization and molecular dynamics with standard molecular mechanics forcefields, such as CHARM (Brooks et al., (1983) J. Comp. Chem., 8: 132) and AMBER 5 (Case et al., (1997), AMBER 5, University of California, San Francisco; Pearlman et al., (1995) Comput. Phys. Commun. 91: 1-41).

[0182] Specialized computer programs can also assist in the process of selecting fragments or chemical entities. These include:

[0183] 1. GRID™ program, version 17 (Goodford, (1985) J. Med. Chem. 28: 849-57), which is available from Molecular Discovery Ltd., Oxford, UK;

[0184] 2. MCSS™ program (Miranker & Karplus, (1991) Proteins 11: 29-34), which is available from Molecular Simulations, Inc., San Diego, Calif.;

[0185] 3. AUTODOCK™ 3.0 program (Goodsell & Olsen, (1990) Proteins 8: 195-202), which is available from the Scripps Research Institute, La Jolla, Calif.;

[0186] 4. DOCK™ 4.0 program (Kuntz et al., (1992) J. Mol. Biol. 161: 269-88), which is available from the University of California, San Francisco, Calif.;

[0187] 5. FLEX-X™ program (See, Rarey et al., (1996) J. Comput. Aid. Mol. Des. 10:41-54), which is available from Tripos, Inc., St. Louis, Miss.;

[0188] 6. MVP program (Lambert, (1997) in Practical Application of Computer-Aided Drug Design, (Charifson, ed.) Marcel-Dekker, New York, pp. 243-303); and

[0189] 7. LUDI™ program (Bohm, (1992) J. Comput. Aid. Mol. Des., 6: 61-78), which is available from Molecular Simulations, Inc., San Diego, Calif.

[0190] Once suitable chemical entities or fragments have been selected, they can be assembled into a single compound or modulator. Assembly can proceed by visual inspection of the relationship of the fragments to each other on the three-dimensional image displayed on a computer screen in relation to the structure coordinates of a PPARα LBD. Manual model building using software such as QUANTA™ or SYBYL™ typically follows.

[0191] Useful programs to aid one of ordinary skill in the art in connecting the individual chemical entities or fragments include:

[0192] 1. CAVEAT™ program (Bartlett et al., (1989) Special Pub:, Royal Chem. Soc. 78: 182-96), which is available from the University of California, Berkeley, Calif.;

[0193] 2. 3D Database systems, such as MACCS-3D™ system program, which is available from MDL Information Systems, San Leandro, Calif. This area is reviewed in Martin, (1992) J. Med. Chem. 35: 2145-54; and

[0194] 3. HOOK™ program (Eisen et al., (1994). Proteins 19: 199-221), which is available from Molecular Simulations, Inc., San Diego, Calif.

[0195] Instead of proceeding to build a PPAR LBD modulator (preferably a PPARα LBD modulator) in a step-wise fashion one fragment or chemical entity at a time as described above, modulatory or other binding compounds can be designed as a whole or de novo using the structural coordinates of a crystalline PPARα LBD polypeptide of the present invention and either an empty binding site or optionally including some portion(s) of a known modulator(s). Applicable methods can employ the following software programs:

[0196] 1. LUDI™ program (Bohm, (1992) J. Comput. Aid. Mol. Des., 6: 61-78), which is available from Molecular Simulations, Inc., San Diego, Calif.;

[0197] 2. LEGEND™ program (Nishibata & Itai, (1991) Tetrahedron 47: 8985); and

[0198] 3. LEAPFROG™, which is available from Tripos Associates, St. Louis, Miss.

[0199] Other molecular modeling techniques can also be employed in accordance with this invention. See, e.g., Cohen et al., (1990) J. Med. Chem. 33: 883-94. See also, Navia & Murcko, (1992) Curr. Opin. Struc. Biol. 2: 202-10; U.S. Pat. No. 6,008,033, herein incorporated by reference.

[0200] Once a compound has been designed or selected by the above methods, the efficiency with which that compound can bind to a PPARα LBD can be tested and optimized by computational evaluation. By way of particular example, a compound that has been designed or selected to function as a PPARα LBD modulator should also preferably traverse a volume not overlapping that occupied by the binding site when it is bound to its native ligand. Additionally, an effective PPAR LBD modulator should preferably demonstrate a relatively small difference in energy between its bound and free states (i.e., a small deformation energy of binding). Thus, the most efficient PPAR LBD modulators should preferably be designed with a deformation energy of binding of not greater than about 10 kcal/mole, and preferably, not greater than 7 kcal/mole. It is possible for PPAR LBD modulators to interact with the polypeptide in more than one conformation that is similar in overall binding energy. In those cases, the deformation energy of binding is taken to be the difference between the energy of the free compound and the average energy of the conformations observed when the modulator binds to the polypeptide.

[0201] A compound designed or selected as binding to a PPAR polypeptide (preferably a PPARα LBD polypeptide) can be further computationally optimized so that in its bound state it would preferably lack repulsive electrostatic interaction with the target polypeptide. Such non-complementary (e.g., electrostatic) interactions include repulsive charge-charge, dipole-dipole and charge-dipole interactions. Specifically, the sum of all electrostatic interactions between the modulator and the polypeptide when the modulator is bound to a PPAR LBD preferably make a neutral or favorable contribution to the enthalpy of binding.

[0202] Specific computer software is available in the art to evaluate compound deformation energy and electrostatic interaction. Examples of programs designed for such uses include:

[0203] 1. Gaussian 98™, which is available from Gaussian, Inc., Pittsburgh, Pa.;

[0204] 2. AMBER™ program, version 6.0, which is available from the University of California at San Francisco;

[0205] 3. QUANTA™ program, which is available from Molecular Simulations, Inc., San Diego, Calif.;

[0206] 4. CHARM® program, which is available from Molecular Simulations, Inc., San Diego, Calif.; and

[0207] 4. Insight II® program, which is available from Molecular Simulations, Inc., San Diego, Calif.

[0208] These programs can be implemented using a suitable computer system. Other hardware systems and software packages will be apparent to those skilled in the art after review of the disclosure of the present invention presented herein.

[0209] Once a PPAR LBD modulating compound has been optimally selected or designed, as described above, substitutions can then be made in some of its atoms or side groups in order to improve or modify its binding properties. Generally, initial substitutions are conservative, i.e., the replacement group will have approximately the same size, shape, hydrophobicity and charge as the original group. It should, of course, be understood that components known in the art to alter conformation should be avoided. Such substituted chemical compounds can then be analyzed for efficiency of fit to a PPAR LBD binding site using the same computer-based approaches described in detail above.

[0210] VIII.B. Distinguishing Between PPAR Subtypes

[0211] The present invention discloses the ability to generate new synthetic ligands to distinguish between PPAR subtypes. As described herein, computer-designed ligands can be generated that distinguish between PPAR subtypes, thereby allowing the generation of either tissue specific or function specific ligands. The atomic structural coordinates disclosed in the present invention reveal structural details unique to PPARα. These structural details can be exploited when a novel ligand is designed using the methods of the present invention or other ligand design methods known in the art. The structural features that differentiate, for example, a PPARα from a PPARγ can be targeted in ligand design. Thus, for example, a ligand can be designed that will recognize PPARα, while not interacting with other PPARs or even with moieties having similar structural features. Prior to the disclosure of the present invention, the ability to target a PPAR subtype was unattainable.

[0212] The present invention also pertains to a method for designing an agonist or modulator with desired levels of activity on the three subtypes, PPARα, PPARγ and PPARδ. In a preferred embodiment, the method comprises obtaining atomic coordinates for structures of the PPARα, PPARγ and/or PPARδ ligand binding domains. The structures can comprise PPARα, PPARγ and PPARδ each bound to various different ligands, and also can comprise structures where no ligand is present. The structures can also comprise models where a compound has been docked into a particular PPAR using a molecular docking procedure, such as the MVP program disclosed herein. Optionally, the structures comprise rotated and translated so as to superimpose corresponding Cα or backbone atoms; this facilitates the comparison of structures.

[0213] The PPARα, PPARγ and PPARδ structures can also be compared using a computer graphics system to identify regions of the ligand binding site that have similar shape and electrostatic character, and to identify regions of the ligand binding site that are narrowed or constricted in one or two of the PPARs compared with the other(s). Since these three PPARs are subject to conformational changes, attention is paid to the range of motion observed for each protein atom over the whole collection of structures. The ligand structures, including both those determined by X-ray crystallography and those modeled using molecular docking procedures, can be examined using a computer graphics system to identify ligands where a chemical modification could increase or decrease binding to a particular PPAR, or decrease activity against a particular PPAR. Additionally or alternatively, the chemical modification can introduce a group into a volume that is normally occupied by an atom of that PPAR.

[0214] Optionally, to selectively decrease activity against a particular PPAR, the chemical modification can be made so as to occupy volume that is normally occupied by atoms of that particular PPAR, but not by atoms of the other PPARs. To increase activity against a particular PPAR, a chemical modification can be made that improves interactions with that particular PPAR. To selectively increase activity against a particular PPAR, a chemical modification can be made that improves the interactions with that particular PPAR, but does not improve the interactions with the other PPARs. Other design principles can also be used to increase or decrease activity on a particular PPAR.

[0215] Thus, various possible compounds and chemical modifications can be considered and compared graphically, and with molecular modeling tools, for synthetic feasibility and likelihood of achieving the desired profile of activation of PPARα, PPARγ and PPARδ. Compounds that appear synthetically feasible and that have a good likelihood of achieving the desired profile are synthesized. The compounds can then be tested for binding and/or activation of PPARα, PPARγ and PPARδ, and tested for their overall biological effect.

[0216] VIII.C. Method of Screening for Chemical and Biological Modulators of the Biological Activity of PPARα

[0217] A candidate substance identified according to a screening assay of the present invention has an ability to modulate the biological activity of a PPAR or a PPAR LBD polypeptide. In a preferred embodiment, such a candidate compound can have utility in the treatment of disorders and conditions associated with the biological activity of a PPARα or a PPARα LBD polypeptide, including lipid homeostasis.

[0218] In a cell-free system, the method comprises the steps of establishing a control system comprising a crystalline PPARα polypeptide and a ligand which is capable of binding to the polypeptide; establishing a test system comprising a crystalline PPARα polypeptide, the ligand, and a candidate compound; and determining whether the candidate compound modulates the activity of the polypeptide by comparison of the test and control systems. A representative ligand comprises Compound 1 or other small molecule, and in this embodiment, the biological activity or property screened includes binding affinity.

[0219] In another embodiment of the invention, a crystalline form of a PPARα polypeptide or a catalytic or immunogenic fragment or oligopeptide thereof, can be used for screening libraries of compounds in any of a variety of drug screening techniques. The fragment employed in such a screening can be affixed to a solid support. The formation of binding complexes, between a crystalline PPARα polypeptide and the agent being tested, will be detected. In a preferred embodiment, the crystalline PPARα polypeptide has an amino acid sequence of SEQ ID NO:2. When a PPARα LBD polypeptide is employed, a preferred embodiment will include a crystalline PPARα polypeptide having the amino acid sequence of SEQ ID NO:4.

[0220] Another technique for drug screening which can be used provides for high throughput screening of compounds having suitable binding affinity to the protein of interest as described in published PCT application WO 84/03564, herein incorporated by reference. In this method, as applied to a crystalline polypeptide of the present invention, large numbers of different small test compounds are synthesized on a solid substrate, such as plastic pins or some other surface. The test compounds are reacted with the crystalline polypeptide, or fragments thereof. Bound polypeptide is then detected by methods well known to those of skill in the art. The crystalline polypeptide can also be placed directly onto plates for use in the aforementioned drug screening techniques.

[0221] In yet another embodiment, a method of screening for a modulator of a PPARα or a PPARα LBD polypeptide comprises: providing a library of test samples; contacting a crystalline form of PPARα or a crystalline form of an PPARα LBD polypeptide with each test sample; detecting an interaction between a test sample and a crystalline form of a PPARα or a crystalline form of a PPARα LBD polypeptide; identifying a test sample that interacts with a crystalline form of a PPARα or a crystalline form of a PPARα LBD polypeptide; and isolating a test sample that interacts with a crystalline form of a PPARα or a crystalline form of a PPARα LBD polypeptide.

[0222] In each of the foregoing embodiments, an interaction can be detected spectrophotometrically, radiologically or immunologically. An interaction between a crystalline form of a PPARα or a crystalline form of a PPARα LBD polypeptide and a test sample can also be quantified using methodology known to those of skill in the art.

[0223] In accordance with the present invention there is also provided a rapid and high throughput screening method that relies on the methods described above. This screening method comprises separately contacting each of a plurality of substantially identical samples with crystalline form of a PPARα or a crystalline form of a PPARα LBD and detecting a resulting binding complex. In such a screening method the plurality of samples preferably comprises more than about 104 samples, or more preferably comprises more than about 5×104 samples.

[0224] VIII.D. Method of Identifying Compounds which Inhibit Ligand Binding

[0225] In one aspect of the present invention, an assay method for identifying a compound that inhibits binding of a ligand to a PPAR polypeptide is disclosed. A ligand of PPARα, such as Compound 1, can be used in the assay method as the ligand against which the inhibition by a test compound is gauged. The method comprises (a) incubating a PPAR polypeptide with a ligand in the presence of a test inhibitor compound; (b) determining an amount of ligand that is bound to the PPAR polypeptide, wherein decreased binding of ligand to the PPAR polypeptide in the presence of the test inhibitor compound relative to binding in the absence of the test inhibitor compound is indicative of inhibition; and (c) identifying the test compound as an inhibitor of ligand binding if decreased ligand binding is observed. Preferably, the ligand is Compound 1.

[0226] In another aspect of the present invention, the disclosed assay method can be used in the structural refinement of candidate PPAR inhibitors. For example, multiple rounds of optimization can be followed by gradual structural changes in a strategy of inhibitor design. A strategy such as this is made possible by the disclosure of the coordinates of the PPARα LBD.

[0227] IX. Design, Preparation and Structural Analysis of Additional PPARα and PPARα LBD Mutants and Structural Equivalents

[0228] The present invention provides for the generation of PPAR and PPAR mutants (preferably PPARα and PPARα LBD mutants), and the ability to solve the crystal structures of those that crystallize. More particularly, through the provision of the three-dimensional structure of a PPARα LBD, desirable sites for mutation can be identified.

[0229] The structure coordinates of a PPARα LBD provided in accordance with the present invention also facilitate the identification of related proteins or enzymes analogous to PPARα in function, structure or both, (for example, a PPARγ) which can lead to novel therapeutic modes for treating or preventing a range of disease states.

[0230] IX.A. Sterically Similar Compounds

[0231] A further aspect of the present invention is that sterically similar compounds can be formulated to mimic the key portions of a PPAR LBD structure. Such compounds are functional equivalents. The generation of a structural functional equivalent can be achieved by the techniques of modeling and chemical design known to those of skill in the art and described herein. Modeling and chemical design of PPAR and PPAR LBD structural equivalents can be based on the structure coordinates of a crystalline PPARα LBD polypeptide of the present invention. It will be understood that all such sterically similar constructs fall within the scope of the present invention.

[0232] IX.B. PPARα Polypeptides

[0233] The generation of chimeric PPAR polypeptides is also an aspect of the present invention. Such a chimeric polypeptide can comprise a PPAR LBD polypeptide or a portion of a PPAR LBD, (e.g. a PPARα LBD) that is fused to a candidate polypeptide or a suitable region of the candidate polypeptide, for example PPARγ. Throughout the present disclosure it is intended that the term “mutant” encompass not only mutants of a PPAR LBD polypeptide but chimeric proteins generated using a PPAR LBD as well. It is thus intended that the following discussion of mutant PPAR LBDs apply mutatis mutandis to chimeric PPAR and PPAR LBD polypeptides and to structural equivalents thereof.

[0234] In accordance with the present invention, a mutation can be directed to a particular site or combination of sites of a wild-type PPAR LBD. For example, an accessory binding site or the binding pocket can be chosen for mutagenesis. Similarly, a residue having a location on, at or near the surface of the polypeptide can be replaced, resulting in an altered surface charge of one or more charge units, as compared to the wild-type PPAR and PPAR LBD. Alternatively, an amino acid residue in a PPAR or a PPAR LBD can be chosen for replacement based on its hydrophilic or hydrophobic characteristics.

[0235] Such mutants can be characterized by any one of several different properties as compared with the wild-type PPAR LBD. For example, such mutants can have an altered surface charge of one or more charge units, or can have an increase in overall stability. Other mutants can have altered substrate specificity in comparison with, or a higher specific activity than, a wild-type PPAR or PPAR LBD.

[0236] PPAR and PPAR LBD mutants of the present invention can be generated in a number of ways. For example, the wild-type sequence of a PPAR or a PPAR LBD can be mutated at those sites identified using this invention as desirable for mutation, by means of oligonucleotide-directed mutagenesis or other conventional methods, such as deletion. Alternatively, mutants of a PPAR or a PPAR LBD can be generated by the site-specific replacement of a particular amino acid with an unnaturally occurring amino acid. In addition, PPAR or PPAR LBD mutants can be generated through replacement of an amino acid residue, for example, a particular cysteine or methionine residue, with selenocysteine or selenomethionine. This can be achieved by growing a host organism capable of expressing either the wild-type or mutant polypeptide on a growth medium depleted of either natural cysteine or methionine (or both) but enriched in selenocysteine or selenomethionine (or both).

[0237] Mutations can be introduced into a DNA sequence coding for a PPAR or a PPAR LBD using synthetic oligonucleotides. These oligonucleotides contain nucleotide sequences flanking the desired mutation sites. Mutations can be generated in the full-length DNA sequence of a PPAR or a PPAR LBD or in any sequence coding for polypeptide fragments of a PPAR or a PPAR LBD.

[0238] According to the present invention, a mutated PPAR or PPAR LBD DNA sequence produced by the methods described above, or any alternative methods known in the art, can be expressed using an expression vector. An expression vector, as is well known to those of skill in the art, typically includes elements that permit autonomous replication in a host cell independent of the host genome, and one or more phenotypic markers for selection purposes. Either prior to or after insertion of the DNA sequences surrounding the desired PPAR or PPAR LBD mutant coding sequence, an expression vector also will include control sequences encoding a promoter, operator, ribosome binding site, translation initiation signal, and, optionally, a repressor gene or various activator genes and a signal for termination. In some embodiments, where secretion of the produced mutant is desired, nucleotides encoding a “signal sequence” can be inserted prior to a PPAR or a PPAR LBD mutant coding sequence. For expression under the direction of the control sequences, a desired DNA sequence must be operatively linked to the control sequences; that is, the sequence must have an appropriate start signal in front of the DNA sequence encoding the PPAR or PPAR LBD mutant, and the correct reading frame to permit expression of that sequence under the control of the control sequences and production of the desired product encoded by that PPAR or PPAR LBD sequence must be maintained.

[0239] Any of a wide variety of well-known available expression vectors can be useful to express a mutated PPAR or PPAR LBD coding sequences of this invention. These include for example, vectors consisting of segments of chromosomal, non-chromosomal and synthetic DNA sequences, such as various known derivatives of SV40, known bacterial plasmids, e.g., plasmids from E. coli including col E1, pCR1, pBR322, pMB9 and their derivatives, wider host range plasmids, e.g., RP4, phage DNAs, e.g., the numerous derivatives of phage λ, e.g., NM 989, and other DNA phages, e.g., M13 and filamentous single stranded DNA phages, yeast plasmids and vectors derived from combinations of plasmids and phage DNAs, such as plasmids which have been modified to employ phage DNA or other expression control sequences. In the preferred embodiments of this invention, vectors amenable to expression in a pRSETA-based expression system are employed. The pRSETA expression system is available from Invitrogen, Inc., Carlsbad, Calif.

[0240] In addition, any of a wide variety of expression control sequences—sequences that control the expression of a DNA sequence when operatively linked to it—can be used in these vectors to express the mutated DNA sequences according to this invention. Such useful expression control sequences, include, for example, the early and late promoters of SV40 for animal cells, the lac system, the trp system the TAC or TRC system, the major operator and promoter regions of phage λ, the control regions of fd coat protein, all for E. coli, the promoter for 3-phosphoglycerate kinase or other glycolytic enzymes, the promoters of acid phosphatase, e.g., Pho5, the promoters of the yeast α-mating factors for yeast, and other sequences known to control the expression of genes of prokaryotic or eukaryotic cells or their viruses, and various combinations thereof.

[0241] A wide variety of hosts are also useful for producing mutated PPARα and PPARα LBD polypeptides according to this invention. These hosts include, for example, bacteria, such as E. coli, Bacillus and Streptomyces, fungi, such as yeasts, and animal cells, such as CHO and COS-1 cells, plant cells, insect cells, such as Sf9 cells, and transgenic host cells.

[0242] It should be understood that not all expression vectors and expression systems function in the same way to express mutated DNA sequences of this invention, and to produce modified PPAR and PPAR LBD polypeptides or PPAR or PPAR LBD mutants. Neither do all hosts function equally well with the same expression system. One of skill in the art can, however, make a selection among these vectors, expression control sequences and hosts without undue experimentation and without departing from the scope of this invention. For example, an important consideration in selecting a vector will be the ability of the vector to replicate in a given host. The copy number of the vector, the ability to control that copy number, and the expression of any other proteins encoded by the vector, such as antibiotic markers, should also be considered.

[0243] In selecting an expression control sequence, a variety of factors should also be considered. These include, for example, the relative strength of the system, its controllability and its compatibility with the DNA sequence encoding a modified PPAR or PPAR LBD polypeptide of this invention, with particular regard to the formation of potential secondary and tertiary structures.

[0244] Hosts should be selected by consideration of their compatibility with the chosen vector, the toxicity of a modified PPAR or PPAR LBD to them, their ability to express mature products, their ability to fold proteins correctly, their fermentation requirements, the ease of purification of a modified PPAR or PPAR LBD and safety. Within these parameters, one of skill in the art can select various vector/expression control system/host combinations that will produce useful amounts of a mutant PPAR or PPAR LBD. A mutant PPAR or PPAR LBD produced in these systems can be purified by a variety of conventional steps and strategies, including those used to purify the wild-type PPAR or PPAR LBD.

[0245] Once a PPAR LBD mutation(s) has been generated in the desired location, such as an active site or dimerization site, the mutants can be tested for any one of several properties of interest. For example, mutants can be screened for an altered charge at physiological pH. This is determined by measuring the mutant PPAR or PPAR LBD isoelectric point (pl) and comparing the observed value with that of the wild-type parent. Isoelectric point can be measured by gel-electrophoresis according to the method of Wellner (Wellner, (1971) Anal. Chem. 43: 597). A mutant PPAR or PPAR LBD polypeptide containing a replacement amino acid located at the surface of the enzyme, as provided by the structural information of this invention, can lead to an altered surface charge and an altered pl.

[0246] IX.C. Generation of an Engineered PPARα LBD or PPARα LBD Mutant

[0247] In another aspect of the present invention, a unique PPAR or PPAR LBD polypeptide can be generated. Such a mutant can facilitate purification and the study of the ligand-binding abilities of a PPAR polypeptide.

[0248] As used in the following discussion, the terms “engineered PPAR”, “engineered PPAR LDB”, “PPAR mutant”, and “PPAR LBD mutant” refers to polypeptides having amino acid sequences which contain at least one mutation in the wild-type sequence. The terms also refer to PPAR and PPAR LBD polypeptides which are capable of exerting a biological effect in that they comprise all or a part of the amino acid sequence of an engineered PPAR or PPAR LBD mutant polypeptide of the present invention, or cross-react with antibodies raised against an engineered PPAR or PPAR LBD mutant polypeptide, or retain all or some or an enhanced degree of the biological activity of the engineered PPAR or PPAR LBD mutant amino acid sequence or protein. Such biological activity can include the binding of small molecules in general, and the binding of Compound 1 in particular.

[0249] The terms “engineered PPAR LBD” and “PPAR LBD mutant” also includes analogs of an engineered PPAR LBD or PPAR LBD mutant polypeptide. By uanalog is intended that a DNA or polypeptide sequence can contain alterations relative to the sequences disclosed herein, yet retain all or some or an enhanced degree of the biological activity of those sequences. Analogs can be derived from genomic nucleotide sequences or from other organisms, or can be created synthetically. Those of skill in the art will appreciate that other analogs, as yet undisclosed or undiscovered, can be used to design and/or construct PPAR LBD or PPAR LBD mutant analogs. There is no need for an engineered PPAR LBD or PPAR LBD mutant polypeptide to comprise all or substantially all of the amino acid sequence of SEQ ID NOs:2 or 4. Shorter or longer sequences are anticipated to be of use in the invention; shorter sequences are herein referred to as “segments”. Thus, the terms “engineered PPAR LBD” and “PPAR LBD mutant” also includes fusion, chimeric or recombinant engineered PPAR LBD or PPAR LBD mutant polypeptides and proteins comprising sequences of the present invention. Methods of preparing such proteins are disclosed herein above and are known in the art.

[0250] IX.D. Sequence Similarity and Identity

[0251] As used herein, the term “substantially similar” means that a particular sequence varies from nucleic acid sequence of SEQ ID NOs:1 or 3, or the amino acid sequence of SEQ ID NOs:2 or 4 by one or more deletions, substitutions, or additions, the net effect of which is to retain at least some of biological activity of the natural gene, gene product, or sequence. Such sequences include “mutant” or “polymorphic” sequences, or sequences in which the biological activity and/or the physical properties are altered to some degree but retains at least some or an enhanced degree of the original biological activity and/or physical properties. In determining nucleic acid sequences, all subject nucleic acid sequences capable of encoding substantially similar amino acid sequences are considered to be substantially similar to a reference nucleic acid sequence, regardless of differences in codon sequences or substitution of equivalent amino acids to create biologically functional equivalents.

[0252] IX.D.1. Sequences that are Substantially Identical to an Engineered PPAR or PPAR LBD Mutant Sequence of the Present Invention

[0253] Nucleic acids that are substantially identical to a nucleic acid sequence of an engineered PPAR or PPAR LBD mutant of the present invention, e.g. allelic variants, genetically altered versions of the gene, etc., bind to an engineered PPAR or PPAR LBD mutant sequence under stringent hybridization conditions. By using probes, particularly labeled probes of DNA sequences, one can isolate homologous or related genes. The source of homologous genes can be any species, e.g. primate species; rodents, such as rats and mice, canines, felines, bovines, equines, yeast, nematodes, etc.

[0254] Between mammalian species, e.g. human and mouse, homologs have substantial sequence similarity, i.e. at least 75% sequence identity between nucleotide sequences. Sequence similarity is calculated based on a reference sequence, which can be a subset of a larger sequence, such as a conserved motif, coding region, flanking region, etc. A reference sequence will usually be at least about 18 nt long, more usually at least about 30 nt long, and can extend to the complete sequence that is being compared. Algorithms for sequence analysis are known in the art, such as BLAST, described in Altschul et al., (1990) J. Mol. Biol. 215: 403-10.

[0255] Percent identity or percent similarity of a DNA or peptide sequence can be determined, for example, by comparing sequence information using the GAP computer program, available from the University of Wisconsin Geneticist Computer Group. The GAP program utilizes the alignment method of Needleman et al., (1970) J. Mol. Biol. 48: 443, as revised by Smith et al., (1981) Adv. Appl. Math. 2:482. Briefly, the GAP program defines similarity as the number of aligned symbols (i.e., nucleotides or amino acids) which are similar, divided by the total number of symbols in the shorter of the two sequences. The preferred parameters for the GAP program are the default parameters, which do not impose a penalty for end gaps. See, e.g., Schwartz et al., eds., (1979), Atlas of Protein Sequence and Structure, National Biomedical Research Foundation, pp. 357-358, and Gribskov et al., (1986) Nucl. Acids. Res. 14: 6745.

[0256] The term “similarity” is contrasted with the term “identity”. Similarity is defined as above; “identity”, however, means a nucleic acid or amino acid sequence having the same amino acid at the same relative position in a given family member of a gene family. Homology and similarity are generally viewed as broader terms than the term identity. Biochemically similar amino acids, for example leucine/isoleucine or glutamate/aspartate, can be present at the same position—these are not identical per se, but are biochemically “similar.” As disclosed herein, these are referred to as conservative differences or conservative substitutions. This differs from a conservative mutation at the DNA level, which changes the nucleotide sequence without making a change in the encoded amino acid, e.g. TCC to TCA, both of which encode serine.

[0257] As used herein, DNA analog sequences are “substantially identical” to specific DNA sequences disclosed herein if: (a) the DNA analog sequence is derived from coding regions of the nucleic acid sequence shown in SEQ ID NOs:1 or 3; or (b) the DNA analog sequence is capable of hybridization with DNA sequences of (a) under stringent conditions and which encode a biologically active PPARα or PPARα LBD gene product; or (c) the DNA sequences are degenerate as a result of alternative genetic code to the DNA analog sequences defined in (a) and/or (b). Substantially identical analog proteins and nucleic acids will have between about 70% and 80%, preferably between about 81% to about 90% or even more preferably between about 91% and 99% sequence identity with the corresponding sequence of the native protein or nucleic acid. Sequences having lesser degrees of identity but comparable biological activity are considered to be equivalents.

[0258] As used herein, “stringent conditions” means conditions of high stringency, for example 6×SSC, 0.2% polyvinylpyrrolidone, 0.2% Ficoll, 0.2% bovine serum albumin, 0.1% sodium dodecyl sulfate, 100 μg/ml salmon sperm DNA and 15% formamide at 68° C. For the purposes of specifying additional conditions of high stringency, preferred conditions are salt concentration of about 200 mM and temperature of about 45° C. One example of such stringent conditions is hybridization at 4×SSC, at 65° C., followed by a washing in 0.1×SSC at 65° C. for one hour. Another exemplary stringent hybridization scheme uses 50% formamide, 4×SSC at 42° C.

[0259] In contrast, nucleic acids having sequence similarity are detected by hybridization under lower stringency conditions. Thus, sequence identity can be determined by hybridization under lower stringency conditions, for example, at 50° C. or higher and 0.1×SSC (9 mM NaCl/0.9 mM sodium citrate) and the sequences will remain bound when subjected to washing at 55° C. in 1×SSC.

[0260] IX.D.2. Complementarity and Hybridization to an Engineered PPARα or PPARα LBD Mutant Sequence

[0261] As used herein, the term “complementary sequences” means nucleic acid sequences which are base-paired according to the standard Watson-Crick complementarity rules. The present invention also encompasses the use of nucleotide segments that are complementary to the sequences of the present invention.

[0262] Hybridization can also be used for assessing complementary sequences and/or isolating complementary nucleotide sequences. As discussed above, nucleic acid hybridization will be affected by such conditions as salt concentration, temperature, or organic solvents, in addition to the base composition, length of the complementary strands, and the number of nucleotide base mismatches between the hybridizing nucleic acids, as will be readily appreciated by those skilled in the art. Stringent temperature conditions will generally include temperatures in excess of about 30° C., typically in excess of about 37° C., and preferably in excess of about 45° C. Stringent salt conditions will ordinarily be less than about 1,000 mM, typically less than about 500 mM, and preferably less than about 200 mM. However, the combination of parameters is much more important than the measure of any single parameter. See, e.g., Wetmur & Davidson, (1968) J. Mol. Biol. 31: 349-70. Determining appropriate hybridization conditions to identify and/or isolate sequences containing high levels of homology is well known in the art. See, e.g., Sambrook et al., (1989) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor, New York.

[0263] IX.D.3. Functional Equivalents of an Engineered PPARα or PPARα LBD Mutant Nucleic Acid Sequence of the Present Invention

[0264] As used herein, the term “functionally equivalent codon” is used to refer to codons that encode the same amino acid, such as the ACG and AGU codons for serine. PPARα or PPARα LBD-encoding nucleic acid sequences comprising SEQ ID NOs:1 and 3 which have functionally equivalent codons are covered by the present invention. Thus, when referring to the sequence example presented in SEQ ID NOs:1 and 3, applicants contemplate substitution of functionally equivalent codons into the sequence example of SEQ ID NOs:1 and 3. Thus, applicants are in possession of amino acid and nucleic acids sequences which include such substitutions but which are not set forth herein in their entirety for convenience.

[0265] It will also be understood by those of skill in the art that amino acid and nucleic acid sequences can include additional residues, such as additional N-or C-terminal amino acids or 5′ or 3′ nucleic acid sequences, and yet still be essentially as set forth in one of the sequences disclosed herein, so long as the sequence retains biological protein activity where polypeptide expression is concerned. The addition of terminal sequences particularly applies to nucleic acid sequences which can, for example, include various non-coding sequences flanking either of the 5′ or 3′ portions of the coding region or can include various internal sequences, i.e., introns, which are known to occur within genes.

[0266] IX.D.4. Biological Equivalents

[0267] The present invention envisions and includes biological equivalents of a engineered PPAR or PPAR LBD mutant polypeptide of the present invention. The term “biological equivalent” refers to proteins having amino acid sequences which are substantially identical to the amino acid sequence of an engineered PPAR LBD mutant of the present invention and which are capable of exerting a biological effect in that they are capable of binding small molecules or cross-reacting with anti- PPAR or PPAR LBD mutant antibodies raised against an engineered mutant PPAR or PPAR LBD polypeptide of the present invention.

[0268] For example, certain amino acids can be substituted for other amino acids in a protein structure without appreciable loss of interactive capacity with, for example, structures in the nucleus of a cell. Since it is the interactive capacity and nature of a protein that defines that protein's biological functional activity, certain amino acid sequence substitutions can be made in a protein sequence (or the nucleic acid sequence encoding it) to obtain a protein with the same, enhanced, or antagonistic properties. Such properties can be achieved by interaction with the normal targets of the protein, but this need not be the case, and the biological activity of the invention is not limited to a particular mechanism of action. It is thus in accordance with the present invention that various changes can be made in the amino acid sequence of an engineered PPAR or PPAR LBD mutant polypeptide of the present invention or its underlying nucleic acid sequence without appreciable loss of biological utility or activity.

[0269] Biologically equivalent polypeptides, as used herein, are polypeptides in which certain, but not most or all, of the amino acids can be substituted. Thus, when referring to the sequence examples presented in SEQ ID NOs:1 and 3, applicants envision substitution of codons that encode biologically equivalent amino acids, as described herein, into the sequence example of SEQ ID NOs:2 and 4, respectively. Thus, applicants are in possession of amino acid and nucleic acids sequences which include such substitutions but which are not set forth herein in their entirety for convenience.

[0270] Alternatively, functionally equivalent proteins or peptides can be created via the application of recombinant DNA technology, in which changes in the protein structure can be engineered, based on considerations of the properties of the amino acids being exchanged, e.g. substitution of lie for Leu. Changes designed by man can be introduced through the application of site-directed mutagenesis techniques, e.g., to introduce improvements to the antigenicity of the protein or to test an engineered PPAR or PPAR LBD mutant polypeptide of the present invention in order to modulate lipid-binding or other activity, at the molecular level.

[0271] Amino acid substitutions, such as those which might be employed in modifying an engineered PPAR or PPAR LBD mutant polypeptide of the present invention are generally, but not necessarily, based on the relative similarity of the amino acid side-chain substituents, for example, their hydrophobicity, hydrophilicity, charge, size, and the like. An analysis of the size, shape and type of the amino acid side-chain substituents reveals that arginine, lysine and histidine are all positively charged residues; that alanine, glycine and serine are all of similar size; and that phenylalanine, tryptophan and tyrosine all have a generally similar shape. Therefore, based upon these considerations, arginine, lysine and histidine; alanine, glycine and serine; and phenylalanine, tryptophan and tyrosine; are defined herein as biologically functional equivalents. Other biologically functionally equivalent changes will be appreciated by those of skill in the art. It is implicit in the above discussion, however, that one of skill in the art can appreciate that a radical, rather than a conservative substitution is warranted in a given situation. Non-conservative substitutions in engineered mutant PPAR or PPAR LBD polypeptides of the present invention are also an aspect of the present invention.

[0272] In making biologically functional equivalent amino acid substitutions, the hydropathic index of amino acids can be considered. Each amino acid has been assigned a hydropathic index on the basis of their hydrophobicity and charge characteristics, these are: isoleucine (+4.5); valine (+4.2); leucine (+3.8); phenylalanine (+2.8); cysteine (+2.5); methionine (+1.9); alanine (+1.8); glycine (−0.4); threonine (−0.7); serine (−0.8); tryptophan (−0.9); tyrosine (−1.3); proline (−1.6); histidine (−3.2); glutamate (−3.5); glutamine (−3.5); aspartate (−3.5); asparagine (−3.5); lysine (−3.9); and arginine (−4.5).

[0273] The importance of the hydropathic amino acid index in conferring interactive biological function on a protein is generally understood in the art (Kyte & Doolittle, (1982), J. Mol. Biol. 157: 105-132, incorporated herein by reference). It is known that certain amino acids can be substituted for other amino acids having a similar hydropathic index or score and still retain a similar biological activity. In making changes based upon the hydropathic index, the substitution of amino acids whose hydropathic indices are within ±2 of the original value is preferred, those which are within ±1 of the original value are particularly preferred, and those within ±0.5 of the original value are even more particularly preferred.

[0274] It is also understood in the art that the substitution of like amino acids can be made effectively on the basis of hydrophilicity. U.S. Pat. No. 4,554,101, incorporated herein by reference, states that the greatest local average hydrophilicity of a protein, as governed by the hydrophilicity of its adjacent amino acids, correlates with its immunogenicity and antigenicity, i.e. with a biological property of the protein. It is understood that an amino acid can be substituted for another having a similar hydrophilicity value and still obtain a biologically equivalent protein.

[0275] As detailed in U.S. Pat. No. 4,554,101, the following hydrophilicity values have been assigned to amino acid residues: arginine (+3.0); lysine (+3.0); aspartate (+3.0±1); glutamate (+3.0±1); serine (+0.3); asparagine (+0.2); glutamine (+0.2); glycine (0); threonine (−0.4); proline (−0.5±1); alanine (−0.5); histidine (−0.5); cysteine (−1.0); methionine (−1.3); valine (−1.5); leucine (−1.8); isoleucine (−1.8); tyrosine (−2.3); phenylalanine (−2.5); tryptophan (−3.4).

[0276] In making changes based upon similar hydrophilicity values, the substitution of amino acids whose hydrophilicity values are within ±2 of the original value is preferred, those which are within ±1 of the original value are particularly preferred, and those within ±0.5 of the original value are even more particularly preferred.

[0277] While discussion has focused on functionally equivalent polypeptides arising from amino acid changes, it will be appreciated that these changes can be effected by alteration of the encoding DNA, taking into consideration also that the genetic code is degenerate and that two or more codons can code for the same amino acid.

[0278] Thus, it will also be understood that this invention is not limited to the particular amino acid and nucleic acid sequences of SEQ ID NOs:1-4. Recombinant vectors and isolated DNA segments can therefore variously include an engineered PPARα or PPARα LBD mutant polypeptide-encoding region itself, include coding regions bearing selected alterations or modifications in the basic coding region, or include larger polypeptides which nevertheless comprise an PPARα or PPARα LBD mutant polypeptide-encoding regions or can encode biologically functional equivalent proteins or polypeptides which have variant amino acid sequences. Biological activity of an engineered PPARα or PPARα LBD mutant polypeptide can be determined, for example, by lipid-binding assays known to those of skill in the art.

[0279] The nucleic acid segments of the present invention, regardless of the length of the coding sequence itself, can be combined with other DNA sequences, such as promoters, enhancers, polyadenylation signals, additional restriction enzyme sites, multiple cloning sites, other coding segments, and the like, such that their overall length can vary considerably. It is therefore contemplated that a nucleic acid fragment of almost any length can be employed, with the total length preferably being limited by the ease of preparation and use in the intended recombinant DNA protocol. For example, nucleic acid fragments can be prepared which include a short stretch complementary to a nucleic acid sequence set forth in SEQ ID NOs:1 and 3, such as about 10 nucleotides, and which are up to 10,000 or 5,000 base pairs in length. DNA segments with total lengths of about 4,000, 3,000, 2,000, 1,000, 500, 200, 100, and about 50 base pairs in length are also useful.

[0280] The DNA segments of the present invention encompass biologically functional equivalents of engineered PPAR or PPAR LBD mutant polypeptides. Such sequences can rise as a consequence of codon redundancy and functional equivalency that are known to occur naturally within nucleic acid sequences and the proteins thus encoded. Alternatively, functionally equivalent proteins or polypeptides can be created via the application of recombinant DNA technology, in which changes in the protein structure can be engineered, based on considerations of the properties of the amino acids being exchanged. Changes can be introduced through the application of site-directed mutagenesis techniques, e.g., to introduce improvements to the antigenicity of the protein or to test variants of an engineered PPAR or PPAR LBD mutant of the present invention in order to examine the degree of lipid-binding activity, or other activity at the molecular level. Various site-directed mutagenesis techniques are known to those of skill in the art and can be employed in the present invention.

[0281] The invention further encompasses fusion proteins and peptides wherein an engineered PPAR or PPAR LBD mutant coding region of the present invention is aligned within the same expression unit with other proteins or peptides having desired functions, such as for purification or immunodetection purposes.

[0282] Recombinant vectors form important further aspects of the present invention. Particularly useful vectors are those in which the coding portion of the DNA segment is positioned under the control of a promoter. The promoter can be that naturally associated with a PPAR gene, as can be obtained by isolating the 5′ non-coding sequences located upstream of the coding segment or exon, for example, using recombinant cloning and/or PCR technology and/or other methods known in the art, in conjunction with the compositions disclosed herein.

[0283] In other embodiments, certain advantages will be gained by positioning the coding DNA segment under the control of a recombinant, or heterologous, promoter. As used herein, a recombinant or heterologous promoter is a promoter that is not normally associated with a PPAR gene in its natural environment. Such promoters can include promoters isolated from bacterial, viral, eukaryotic, or mammalian cells. Naturally, it will be important to employ a promoter that effectively directs the expression of the DNA segment in the cell type chosen for expression. The use of promoter and cell type combinations for protein expression is generally known to those of skill in the art of molecular biology (See, e.g., Sambrook et al., (1989) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York, specifically incorporated herein by reference). The promoters employed can be constitutive or inducible and can be used under the appropriate conditions to direct high level expression of the introduced DNA segment, such as is advantageous in the large-scale production of recombinant proteins or peptides. One preferred promoter system contemplated for use in high-level expression is a T7 promoter-based system.

[0284] X. The Role of the Three-Dimensional Structure of the PPARα LDB in Solving Additional PPAR Crystals

[0285] Because polypeptides can crystallize in more than one crystal form, the structural coordinates of a PPARα LBD, or portions thereof, as provided by the present invention, are particularly useful in solving the structure of other crystal forms of PPARα and the crystalline forms of other PPARs. The coordinates provided in the present invention can also be used to solve the structure of PPAR or PPAR LBD mutants (such as those described in Section IX above), PPAR LDB co-complexes, or of the crystalline form of any other protein with significant amino acid sequence homology to any functional domain of PPAR.

[0286] X.A. Determining the Three-Dimensional Structure of a Polypeptide Using the Three-Dimensional Structure of the PPARα LBD as a Template in Molecular Replacement

[0287] One method that can be employed for the purpose of solving additional PPAR crystal structures is molecular replacement. See generally, Rossmann, ed, (1972) The Molecular Replacement Method, Gordon & Breach, New York. In the molecular replacement method, the unknown crystal structure, whether it is another crystal form of a PPARα or a PPARα LBD, (i.e. a PPARα or a PPARα LBD mutant), or a PPARα or a PPARα LBD polypeptide complexed with another compound (a “co-complex”), or the crystal of some other protein with significant amino acid sequence homology to any functional region of the PPARα LBD, can be determined using the PPARα LBD structure coordinates provided in Table 2. This method provides an accurate structural form for the unknown crystal more quickly and efficiently than attempting to determine such information ab initio.

[0288] In addition, in accordance with this invention, PPARα or PPARα LBD mutants can be crystallized in complex with known modulators. The crystal structures of a series of such complexes can then be solved by molecular replacement and compared with that of wild-type PPARα or the wild-type PPARα LBD. Potential sites for modification within the various binding sites of the enzyme can thus be identified. This information provides an additional tool for determining the most efficient binding interactions, for example, increased hydrophobic interactions, between the PPARα LBD and a chemical entity or compound.

[0289] All of the complexes referred to in the present disclosure can be studied using X-ray diffraction techniques (See, e.g., Blundell & Johnson (1985) Method.Enzymol., 114A & 115B, (Wyckoff et al., eds.), Academic Press) and can be refined using computer software, such as the X-PLOR™ program (Brünger, (1992) X-PLOR, Version 3.1. A System for X-ray Crystallography and NMR, Yale University Press, New Haven, Conn.; X-PLOR is available from Molecular Simulations, Inc., San Diego, Calif.). This information can thus be used to optimize known classes of PPAR and PPAR LBD modulators, and more importantly, to design and synthesize novel classes of PPAR and PPAR LBD modulators.

LABORATORY EXAMPLES

[0290] The following Laboratory Examples have been included to illustrate preferred modes of the invention. Certain aspects of the following Laboratory Examples are described in terms of techniques and procedures found or contemplated by the present inventors to work well in the practice of the invention. These Laboratory Examples are exemplified through the use of standard laboratory practices of the inventors. In light of the present disclosure and the general level of skill in the art, those of skill will appreciate that the following Laboratory Examples are intended to be exemplary only and that numerous changes, modifications and alterations can be employed without departing from the spirit and scope of the invention.

Laboratory Example 1

Protein Preparation

[0291] The nucleic acid sequence encoding the PPARα ligand binding domain (amino acids 192-468) tagged with MKKGHHHHHHG (SEQ ID NO: 9) was operatively linked to and expressed using the T7 promoter of plasmid vector pRSETA. BL21 (DE3) E. coli cells transformed with this expression vector were grown at 24° C. in shaker flasks for 66 hours on 2xYT medium (16 g/L Bacto-Tryptone, 10 g/L yeast extract, 5 g/L NaCl, QC with distilled water) with 50 mg/L carbenicillin to an OD600 of approximately 9.0. The cells were harvested, resuspended with 20 ml extract Buffer (20 mM HEPES, pH 7.5, 50 mM imidozle, 250 mM NaCl and a pinch of lysozyme) per liter of cells and were lysed by sonication for 20 minutes on ice. The lysed cells were centrifuged at 40,000 g for 40 minutes and the supematant was loaded on a 100 ml Ni-agarose column.

[0292] The column was washed with 150 ml Buffer A (10% glycerol, 20 mM HEPES pH 7.5, 25 mM imidizole) and the protein was eluted with a 450 ml gradient of Buffer B (10% glycerol, 20 mM HEPES pH 7.5, 500 mM imidozle). The protein, which eluted at 20% Buffer B, was diluted with one volume of Buffer C (20 mM HEPES, pH 7.5, 1 mM EDTA), and loaded on an 100 ml S-Sepharose™ (Pharmacia, Peapack, N.J.) column. The column was washed with a 100 ml Buffer C and the PPARα LBD protein was eluted with a 200 ml gradient of Buffer D (20 mM HEPES, pH 7.5, 10 mM DTT, 1 M ammonium acetate). The PPAR alpha LBD eluted from the column at 43% Buffer D. The protein yield was 9 mg/L of cells grown and was >95% pure, as determined by SDS-PAGE analysis.

[0293] The protein was then diluted to 1 mg/ml with Buffer C such that the final buffer composition was 220 mM ammonium acetate, 20 mM HEPES pH 7.5, 1 mM EDTA and 1 mM DTT. The diluted protein was aliquoted into 9 ml aliquots, flash frozen with liquid nitrogen and stored at −80° C. To prepare complexes an individual aliquot was thawed for each compound. The peptide SRC1 (See, Xu et al., (1999) Mol. Cell 3: 397-403) was added in a mol ratio of 1.5 as a 2 mg/100 μl DMSO stock. The peptide was then added in a mol ratio of 5:1 as a 2 mg/100 μl DMSO stock and spun at 4K for 20 min to clarify the solution before concentrating in Centriprep™ 30 filtration units (Millipore, Bedford, Mass.). The solution containing the PPARα LBD-SRC1 complexes was concentrated to approximately 10 mg/ml with 80% yield. The complexes were then aliquoted in single use aliquots of 30 μl, flash frozen in liquid nitrogen and stored at −80° C.

Laboratory Example 2

Crystallization and Data Collection

[0294] The crystals disclosed in this invention were grown at room temperature using the hanging drop vapor diffusion method. The hanging drops comprised 1 μl of the above protein-ligand solutions, and were mixed with an equal volume (1 μl) of well buffer comprising 7% PEG 3350, 200 mM NaF, and 12% 2,5 hexanediol.

[0295] Before data collection, crystals were transiently mixed with well buffer that contained an additional 10% hexanediol as a cryoprotectant, and then flash frozen in liquid nitrogen.

[0296] The PPARα crystals formed in the P21212 space group, with a=61.3 Å, b=103.5 Å, c=49.9 Å. Each asymmetry unit contained a single PPARα LBD with 45% solvent content. Crystals contained Compound 1, the PPARα LBD and SRC1 peptide, in a ratio of 1:1:1. Data were collected with a Rigaku R-Axis II (Rigaku, Tokyo, Japan) detector in house, or with a MAR CCD detector in the IMCA 17ID beam line at the Argonne National Laboratory (Argonne, Ill.), and the observed reflections were reduced, merged and scaled with DENZO™ and SCALEPACK™ in the HKL2000 package (Otwinowski, (1993) in Proceedings of the CCP4 Study Weekend: Data Collection and Processing. (Sawyer et al., eds.), pp.56-62, SERC Daresbury Laboratory, England).

Laboratory Example 3

Structure Determination and Refinement

[0297] The structure was determined by molecular replacement methods with the CCP4 AmoRe program (Collaborative Computational Project Number 4, 1994; Navaza, (1994) Acta. Cryst. A50: 157-163) using the structure coordinates for the PPARδ LBD (Xu et al., (1999) Mol. Cell 3: 397-403), residues 167-441, as the initial model (Table 3). The best fitting solution gave a correlation coefficiency of 70% and an R-factor of 33%. Model building was performed with the software program QUANTA™, and structure refinement was achieved using the CNS software program (Brünger et al., (1998) Acta. Crystallogr. D54: 905-921). Structure refinement involved multiple cycles of manual rebuilding. The final structure (Table 2 and FIGS. 1, 2, 4 and 7) includes one PPARα LBD, one SRC1 peptide and Compound 1. The statistics of the structures are summarized in Table 1.

Laboratory Example 4

Computational Analysis

[0298] Surface areas were calculated using both the Connolly MS program (Connolly, (1983) Science 221: 709-713) and the MVP program (Lambert, (1997) in Practical Application of Computer-Aided Drug Design, (Charifson, ed.), pp. 243-303, Marcel-Dekker, New York). The C2-symmetry axis, sequence alignments and binding site accessible waters were calculated using the software program MVP.

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4TABLE 1PARAMETERS FOR THE CRYSTALLINE FORMOF THE LIGAND BINDING DOMAIN (RESIDUES207-441) OF PPARα IN COMPLEX WITHCOMPOUND 1X-ray SourceGlaxo FacilityIMCASpace GroupP21212P21212Resolution (Å)20.0-2.420.0-1.8Unique Reflections (N)64,77230,147Completeness (%)95.299.4I/σ(last shell)25.4 (3.3)39.5 (5.2)Rsyma (%)9.44.5Refinement StatisticsR factorb (%)(2σ)22.9R freec (%)(2σ)26.9R.M.S.D. BondLengths (Å)0.010R.M.S.D. BondAngles (degrees)1.357Number of H2O Molecules396Total Non-hydrogen Atoms2659r.m.s.d. is the root mean square deviation from ideal geometry. aRsym = Σ | Iavg − Ii |/Σ Ii bRfactor = Σ | FP − FPcalc |/Σ Fp, where Fp and Fpcalc are observed and calculated structure factors, respectively cRfree is calculated from a randomly chosen 10% of reflections that have never been used in refinement, and Rfactor is calculated for the remaining 90% of reflections.

[0388]

5

TABLE 2

ATOMIC STRUCTURE COORDINATE DATA OBTAINED FROM X-RAY

DIFRACTION FROM THE LIGAND BINDING DOMAIN OF PPARα in

COMPLEX WITH COUPOUND 1

ATOM

ATOM
TYPE
RESIDUE
PROTEIN #
#
X
Y
Z
OCC
B

1
CB
ASP
A
202
14.533
5.575
19.857
1.00
78.46

2
CG
ASP
A
202
14.270
4.099
20.079
1.00
79.53

3
OD1
ASP
A
202
13.370
3.547
19.410
1.00
80.23

4
OD2
ASP
A
202
14.963
3.492
20.921
1.00
80.14

5
C
ASP
A
202
15.243
7.375
18.274
1.00
76.33

6
O
ASP
A
202
14.377
8.174
17.918
1.00
76.50

7
N
ASP
A
202
16.101
5.066
18.013
1.00
77.36

8
CA
ASP
A
202
14.925
5.890
18.412
1.00
77.08

9
N
LEU
A
203
16.488
7.739
18.565
1.00
74.80

10
CA
LEU
A
203
16.927
9.125
18.460
1.00
72.96

11
CB
LEU
A
203
18.150
9.378
19.344
1.00
73.58

12
CG
LEU
A
203
18.821
10.740
19.132
1.00
73.64

13
CD1
LEU
A
203
18.061
11.815
19.895
1.00
73.44

14
CD2
LEU
A
203
20.265
10.680
19.597
1.00
73.65

15
C
LEU
A
203
17.304
9.418
17.019
1.00
71.55

16
O
LEU
A
203
17.251
10.561
16.574
1.00
71.54

17
N
LYS
A
204
17.694
8.379
16.292
1.00
69.51

18
CA
LYS
A
204
18.088
8.548
14.905
1.00
67.63

19
CB
LYS
A
204
18.876
7.324
14.439
1.00
68.39

20
CG
LYS
A
204
19.491
7.454
13.057
1.00
68.94

21
CD
LYS
A
204
20.927
6.946
13.047
1.00
69.41

22
CE
LYS
A
204
21.072
5.632
13.805
1.00
69.58

23
NZ
LYS
A
204
22.447
5.088
13.716
1.00
70.30

24
C
LYS
A
204
16.866
8.787
14.025
1.00
65.91

25
O
LYS
A
204
16.995
9.160
12.858
1.00
66.04

26
N
SER
A
205
15.680
8.574
14.590
1.00
62.82

27
CA
SER
A
205
14.445
8.814
13.854
1.00
59.48

28
CB
SER
A
205
13.240
8.252
14.613
1.00
59.65

29
OG
SER
A
205
12.994
8.984
15.802
1.00
59.47

30
C
SER
A
205
14.330
10.331
13.751
1.00
56.82

31
O
SER
A
205
13.495
10.861
13.016
1.00
56.27

32
N
LEU
A
206
15.186
11.015
14.510
1.00
53.62

33
CA
LEU
A
206
15.240
12.473
14.540
1.00
50.75

34
CB
LEU
A
206
16.362
12.935
15.477
1.00
50.59

35
CG
LEU
A
206
16.728
14.421
15.542
1.00
49.94

36
CD1
LEU
A
206
15.575
15.224
16.114
1.00
49.18

37
CD2
LEU
A
206
17.972
14.595
16.403
1.00
49.63

38
C
LEU
A
206
15.490
13.018
13.142
1.00
48.97

39
O
LEU
A
206
15.015
14.098
12.795
1.00
49.11

40
N
ALA
A
207
16.239
12.262
12.344
1.00
46.47

41
CA
ALA
A
207
16.555
12.671
10.983
1.00
45.03

42
CB
ALA
A
207
17.428
11.622
10.313
1.00
44.87

43
C
ALA
A
207
15.291
12.907
10.157
1.00
44.53

44
O
ALA
A
207
15.077
14.006
9.646
1.00
43.47

45
N
LYS
A
208
14.454
11.881
10.029
1.00
43.76

46
CA
LYS
A
208
13.226
12.011
9.251
1.00
42.20

47
CB
LYS
A
208
12.471
10.680
9.194
1.00
44.47

48
CG
LYS
A
208
11.537
10.576
7.990
1.00
45.43

49
CD
LYS
A
208
10.715
9.300
7.999
1.00
46.92

50
CE
LYS
A
208
9.660
9.328
9.093
1.00
48.09

51
NZ
LYS
A
208
8.799
8.114
9.059
1.00
49.24

52
C
LYS
A
208
12.330
13.086
9.852
1.00
41.19

53
O
LYS
A
208
11.658
13.818
9.128
1.00
40.18

54
N
ARG
A
209
12.328
13.174
11.179
1.00
38.94

55
CA
ARG
A
209
11.535
14.172
11.887
1.00
37.26

56
CB
ARG
A
209
11.745
14.022
13.398
1.00
39.88

57
CG
ARG
A
209
11.394
15.257
14.226
1.00
43.03

58
CD
ARG
A
209
9.901
15.543
14.240
1.00
45.71

59
NE
ARG
A
209
9.622
16.898
14.711
1.00
46.98

60
CZ
ARG
A
209
8.403
17.416
14.828
1.00
47.56

61
NH1
ARG
A
209
7.337
16.691
14.511
1.00
48.63

62
NH2
ARG
A
209
8.251
18.662
15.255
1.00
47.03

63
C
ARG
A
209
11.945
15.575
11.437
1.00
34.87

64
O
ARG
A
209
11.104
16.388
11.050
1.00
33.63

65
N
ILE
A
210
13.243
15.855
11.496
1.00
31.60

66
CA
ILE
A
210
13.759
17.156
11.086
1.00
28.45

67
CB
ILE
A
210
15.283
17.260
11.355
1.00
27.35

68
CG2
ILE
A
210
15.873
18.457
10.625
1.00
26.86

69
CG1
ILE
A
210
15.532
17.376
12.863
1.00
27.32

70
CD1
ILE
A
210
17.002
17.319
13.251
1.00
26.22

71
C
ILE
A
210
13.485
17.354
9.599
1.00
27.44

72
O
ILE
A
210
13.158
18.453
9.157
1.00
26.71

73
N
TYR
A
211
13.614
16.277
8.836
1.00
25.68

74
CA
TYR
A
211
13.370
16.335
7.403
1.00
26.73

75
CB
TYR
A
211
13.782
15.011
6.748
1.00
25.17

76
OG
TYR
A
211
13.657
14.971
5.236
1.00
27.92

77
CD1
TYR
A
211
13.862
16.116
4.464
1.00
27.10

78
CE1
TYR
A
211
13.787
16.071
3.073
1.00
27.40

79
CD2
TYR
A
211
13.372
13.775
4.573
1.00
28.20

80
CE2
TYR
A
211
13.296
13.721
3.180
1.00
29.60

81
CZ
TYR
A
211
13.506
14.875
2.437
1.00
28.67

82
OH
TYR
A
211
13.446
14.829
1.061
1.00
30.22

83
C
TYR
A
211
11.892
16.637
7.152
1.00
26.35

84
O
TYR
A
211
11.552
17.402
6.253
1.00
22.94

85
N
GLU
A
212
11.010
16.046
7.951
1.00
27.41

86
CA
GLU
A
212
9.586
16.299
7.778
1.00
27.15

87
CB
GLU
A
212
8.760
15.392
8.700
1.00
29.37

88
CG
GLU
A
212
8.870
13.917
8.324
1.00
32.72

89
CD
GLU
A
212
7.948
13.014
9.129
1.00
34.56

90
OE1
GLU
A
212
8.053
12.998
10.372
1.00
36.22

91
OE2
GLU
A
212
7.121
12.314
8.510
1.00
36.44

92
C
GLU
A
212
9.297
17.771
8.057
1.00
25.89

93
O
GLU
A
212
8.535
18.407
7.331
1.00
25.26

94
N
ALA
A
213
9.926
18.312
9.099
1.00
23.75

95
CA
ALA
A
213
9.746
19.712
9.461
1.00
22.66

96
CB
ALA
A
213
10.524
20.026
10.731
1.00
24.94

97
C
ALA
A
213
10.221
20.609
8.321
1.00
21.68

98
O
ALA
A
213
9.618
21.642
8.033
1.00
20.08

99
N
TYR
A
214
11.308
20.203
7.676
1.00
20.59

100
CA
TYR
A
214
11.873
20.956
6.563
1.00
20.21

101
CB
TYR
A
214
13.226
20.343
6.204
1.00
21.59

102
CG
TYR
A
214
13.895
20.850
4.950
1.00
20.23

103
CD1
TYR
A
214
13.565
20.322
3.701
1.00
21.49

104
CE1
TYR
A
214
14.259
20.692
2.557
1.00
20.65

105
CD2
TYR
A
214
14.933
21.779
5.019
1.00
19.83

106
CE2
TYR
A
214
15.635
22.156
3.877
1.00
20.40

107
CZ
TYR
A
214
15.295
21.603
2.651
1.00
20.09

108
OH
TYR
A
214
16.013
21.932
1.522
1.00
22.28

109
C
TYR
A
214
10.920
20.963
5.364
1.00
20.36

110
O
TYR
A
214
10.663
22.009
4.768
1.00
18.08

111
N
LEU
A
215
10.370
19.801
5.027
1.00
19.65

112
CA
LEU
A
215
9.453
19.720
3.896
1.00
21.64

113
CB
LEU
A
215
9.161
18.255
3.563
1.00
22.15

114
CG
LEU
A
215
10.347
17.450
3.031
1.00
23.81

115
CD1
LEU
A
215
9.934
15.993
2.840
1.00
24.83

116
CD2
LEU
A
215
10.824
18.055
1.711
1.00
24.52

117
C
LEU
A
215
8.144
20.462
4.161
1.00
21.59

118
O
LEU
A
215
7.521
20.994
3.246
1.00
22.21

119
N
LYS
A
216
7.730
20.509
5.419
1.00
21.23

120
CA
LYS
A
216
6.484
21.177
5.773
1.00
24.07

121
CB
LYS
A
216
5.974
20.611
7.107
1.00
27.04

122
CG
LYS
A
216
4.766
21.320
7.718
1.00
32.48

123
CD
LYS
A
216
5.177
22.541
8.536
1.00
34.35

124
CE
LYS
A
216
3.978
23.177
9.227
1.00
36.46

125
NZ
LYS
A
216
4.372
24.346
10.068
1.00
35.63

126
C
LYS
A
216
6.574
22.701
5.863
1.00
23.63

127
O
LYS
A
216
5.584
23.401
5.619
1.00
22.64

128
N
ASN
A
217
7.758
23.216
6.178
1.00
21.43

129
CA
ASN
A
217
7.922
24.655
6.371
1.00
21.60

130
CB
ASN
A
217
8.627
24.894
7.708
1.00
21.30

131
CG
ASN
A
217
7.734
24.576
8.887
1.00
21.85

132
OD1
ASN
A
217
6.763
25.286
9.144
1.00
21.90

133
ND2
ASN
A
217
8.041
23.493
9.596
1.00
21.00

134
C
ASN
A
217
8.576
25.515
5.304
1.00
20.24

135
O
ASN
A
217
8.485
26.741
5.369
1.00
21.01

136
N
PHE
A
218
9.226
24.902
4.324
1.00
19.71

137
CA
PHE
A
218
9.880
25.682
3.275
1.00
20.43

138
CB
PHE
A
218
11.352
25.283
3.158
1.00
19.13

139
CG
PHE
A
218
12.161
25.595
4.388
1.00
18.17

140
CD1
PHE
A
218
12.350
26.917
4.793
1.00
16.25

141
CD2
PHE
A
218
12.734
24.574
5.136
1.00
16.60

142
CE1
PHE
A
218
13.098
27.211
5.925
1.00
16.71

143
CE2
PHE
A
218
13.486
24.856
6.273
1.00
17.69

144
CZ
PHE
A
218
13.671
26.177
6.671
1.00
18.05

145
C
PHE
A
218
9.185
25.502
1.935
1.00
21.87

146
O
PHE
A
218
9.159
24.408
1.388
1.00
23.21

147
N
ASN
A
219
8.632
26.587
1.407
1.00
22.66

148
CA
ASN
A
219
7.927
26.530
0.136
1.00
23.56

149
CB
ASN
A
219
7.238
27.869
−0.135
1.00
26.95

150
CG
ASN
A
219
6.044
28.101
0.785
1.00
29.92

151
OD1
ASN
A
219
5.119
27.283
0.836
1.00
33.43

152
ND2
ASN
A
219
6.058
29.211
1.513
1.00
32.80

153
C
ASN
A
219
8.836
26.142
−1.026
1.00
23.59

154
O
ASN
A
219
8.374
25.604
−2.029
1.00
22.24

155
N
MET
A
220
10.129
26.413
−0.888
1.00
22.41

156
CA
MET
A
220
11.083
26.059
−1.927
1.00
23.18

157
CB
MET
A
220
11.713
27.316
−2.535
1.00
23.66

158
CG
MET
A
220
12.713
27.051
−3.664
1.00
25.31

159
SD
MET
A
220
11.971
26.305
−5.126
1.00
26.48

160
CE
MET
A
220
10.935
27.658
−5.694
1.00
24.83

161
C
MET
A
220
12.173
25.185
−1.329
1.00
23.23

162
O
MET
A
220
12.639
25.434
−0.214
1.00
23.23

163
N
ASN
A
221
12.549
24.147
−2.064
1.00
21.71

164
CA
ASN
A
221
13.610
23.245
−1.638
1.00
22.22

165
CB
ASN
A
221
13.049
22.029
−0.891
1.00
23.15

166
CG
ASN
A
221
12.074
21.224
−1.719
1.00
24.30

167
OD1
ASN
A
221
12.329
20.923
−2.880
1.00
25.96

168
ND2
ASN
A
221
10.954
20.851
−1.113
1.00
26.83

169
C
ASN
A
221
14.366
22.825
−2.889
1.00
22.09

170
O
ASN
A
221
13.994
23.218
−3.995
1.00
20.57

171
N
LYS
A
222
15.415
22.028
−2.724
1.00
20.59

172
CA
LYS
A
222
16.232
21.614
−3.858
1.00
20.89

173
CB
LYS
A
222
17.466
20.859
−3.361
1.00
21.48

174
CG
LYS
A
222
18.653
20.954
−4.297
1.00
20.77

175
CD
LYS
A
222
19.922
20.502
−3.602
1.00
21.19

176
CE
LYS
A
222
21.125
20.628
−4.507
1.00
21.09

177
NZ
LYS
A
222
22.361
20.180
−3.823
1.00
19.55

178
C
LYS
A
222
15.502
20.789
−4.914
1.00
20.69

179
O
LYS
A
222
15.678
21.022
−6.109
1.00
19.10

180
N
VAL
A
223
14.689
19.827
−4.493
1.00
20.29

181
CA
VAL
A
223
13.954
19.023
−5.463
1.00
23.64

182
CB
VAL
A
223
13.004
18.016
−4.776
1.00
25.30

183
CG1
VAL
A
223
12.236
17.229
−5.831
1.00
28.94

184
CG2
VAL
A
223
13.795
17.073
−3.900
1.00
28.35

185
C
VAL
A
223
13.125
19.930
−6.375
1.00
22.27

186
O
VAL
A
223
13.228
19.844
−7.600
1.00
22.87

187
N
LYS
A
224
12.314
20.797
−5.769
1.00
22.90

188
CA
LYS
A
224
11.460
21.724
−6.518
1.00
22.56

189
CB
LYS
A
224
10.640
22.604
−5.563
1.00
25.17

190
CG
LYS
A
224
9.512
21.908
−4.818
1.00
25.33

191
CD
LYS
A
224
8.688
22.947
−4.060
1.00
27.14

192
CE
LYS
A
224
7.467
22.352
−3.391
1.00
27.11

193
NZ
LYS
A
224
6.651
23.419
−2.738
1.00
25.12

194
C
LYS
A
224
12.254
22.635
−7.453
1.00
23.61

195
O
LYS
A
224
11.896
22.815
−8.622
1.00
22.28

196
N
ALA
A
225
13.329
23.215
−6.929
1.00
22.21

197
CA
ALA
A
225
14.174
24.112
−7.709
1.00
21.88

198
CB
ALA
A
225
15.237
24.738
−6.808
1.00
19.12

199
C
ALA
A
225
14.843
23.420
−8.896
1.00
22.78

200
O
ALA
A
225
14.863
23.960
−10.000
1.00
23.11

201
N
ARG
A
226
15.397
22.231
−8.675
1.00
23.76

202
CA
ARG
A
226
16.067
21.514
−9.753
1.00
26.20

203
CB
ARG
A
226
16.732
20.242
−9.215
1.00
27.83

204
CG
ARG
A
226
18.056
20.526
−8.517
1.00
28.58

205
CD
ARG
A
226
19.012
21.239
−9.467
1.00
32.23

206
NE
ARG
A
226
19.998
22.056
−8.766
1.00
34.36

207
CZ
ARG
A
226
19.683
23.053
−7.942
1.00
37.04

208
NH1
ARG
A
226
18.409
23.345
−7.713
1.00
39.09

209
NH2
ARG
A
226
20.636
23.772
−7.365
1.00
35.24

210
C
ARG
A
226
15.150
21.185
−10.926
1.00
27.67

211
O
ARG
A
226
15.590
21.176
−12.079
1.00
29.64

212
N
VAL
A
227
13.879
20.922
−10.639
1.00
27.53

213
CA
VAL
A
227
12.918
20.627
−11.697
1.00
28.83

214
CB
VAL
A
227
11.548
20.219
−11.120
1.00
30.09

215
CG1
VAL
A
227
10.500
20.186
−12.229
1.00
31.75

216
CG2
VAL
A
227
11.653
18.851
−10.464
1.00
31.01

217
C
VAL
A
227
12.728
21.878
−12.543
1.00
28.74

218
O
VAL
A
227
12.736
21.825
−13.775
1.00
27.81

219
N
ILE
A
228
12.561
23.010
−11.868
1.00
26.31

220
CA
ILE
A
228
12.365
24.283
−12.548
1.00
26.14

221
CB
ILE
A
228
12.050
25.398
−11.520
1.00
24.59

222
CG2
ILE
A
228
11.998
26.764
−12.200
1.00
23.06

223
CG1
ILE
A
228
10.720
25.094
−10.831
1.00
23.57

224
CD1
ILE
A
228
10.401
26.010
−9.661
1.00
25.78

225
C
ILE
A
228
13.592
24.671
−13.373
1.00
28.37

226
O
ILE
A
228
13.465
25.234
−14.462
1.00
27.38

227
N
LEU
A
229
14.776
24.355
−12.856
1.00
28.44

228
CA
LEU
A
229
16.027
24.684
−13.533
1.00
31.74

229
CB
LEU
A
229
17.156
24.801
−12.509
1.00
30.50

230
CG
LEU
A
229
17.045
25.984
−11.544
1.00
30.22

231
CD1
LEU
A
229
18.042
25.823
−10.405
1.00
29.46

232
CD2
LEU
A
229
17.290
27.279
−12.304
1.00
29.52

233
C
LEU
A
229
16.424
23.685
−14.616
1.00
34.68

234
O
LEU
A
229
17.281
23.974
−15.450
1.00
35.11

235
N
SER
A
230
15.808
22.509
−14.591
1.00
37.91

236
CA
SER
A
230
16.096
21.472
−15.574
1.00
42.67

237
CB
SER
A
230
17.416
20.768
−15.261
1.00
42.74

238
OG
SER
A
230
18.460
21.252
−16.085
1.00
44.54

239
C
SER
A
230
14.987
20.443
−15.629
1.00
45.44

240
O
SER
A
230
14.592
19.875
−14.613
1.00
46.52

241
N
GLY
A
231
14.491
20.203
−16.832
1.00
48.97

242
CA
GLY
A
231
13.427
19.242
−17.011
1.00
52.46

243
C
GLY
A
231
12.702
19.563
−18.294
1.00
55.01

244
O
GLY
A
231
12.343
18.658
−19.040
1.00
55.62

245
N
LYS
A
232
12.510
20.860
−18.542
1.00
57.05

246
CA
LYS
A
232
11.828
21.367
−19.732
1.00
58.42

247
CB
LYS
A
232
12.757
21.290
−20.945
1.00
59.37

248
CG
LYS
A
232
13.834
22.365
−20.980
1.00
58.74

249
CD
LYS
A
232
14.914
22.004
−21.989
1.00
59.57

250
CE
LYS
A
232
15.909
23.134
−22.205
1.00
59.20

251
NZ
LYS
A
232
15.454
24.073
−23.261
1.00
60.11

252
C
LYS
A
232
10.518
20.651
−20.036
1.00
59.28

253
O
LYS
A
232
9.537
21.285
−20.416
1.00
59.75

254
N
ALA
A
233
10.525
19.331
−19.869
1.00
60.20

255
CA
ALA
A
233
9.371
18.469
−20.097
1.00
60.65

256
CB
ALA
A
233
9.187
17.529
−18.907
1.00
60.60

257
C
ALA
A
233
8.110
19.284
−20.312
1.00
61.11

258
O
ALA
A
233
7.648
19.450
−21.442
1.00
61.12

259
N
SER
A
234
7.564
19.799
−19.217
1.00
61.07

260
CA
SER
A
234
6.360
20.609
−19.281
1.00
61.06

261
CB
SER
A
234
5.742
20.748
−17.885
1.00
61.00

262
OG
SER
A
234
4.582
21.563
−17.917
1.00
59.89

263
C
SER
A
234
6.687
21.988
−19.847
1.00
61.10

264
O
SER
A
234
7.344
22.107
−20.883
1.00
61.74

265
N
ASN
A
235
6.230
23.026
−19.157
1.00
60.20

266
CA
ASN
A
235
6.452
24.396
−19.590
1.00
59.10

267
CD
ASN
A
235
5.740
24.614
−20.934
1.00
58.65

268
CG
ASN
A
235
5.584
26.076
−21.296
1.00
58.90

269
OD1
ASN
A
235
4.628
26.728
−20.872
1.00
59.73

270
ND2
ASN
A
235
6.521
26.601
−22.081
1.00
58.39

271
C
ASN
A
235
5.952
25.349
−18.502
1.00
58.52

272
O
ASN
A
235
5.697
24.917
−17.377
1.00
59.67

273
N
ASN
A
236
5.807
26.629
−18.840
1.00
56.14

274
CA
ASN
A
236
5.393
27.666
−17.896
1.00
51.26

275
CB
ASN
A
236
4.356
27.117
−16.912
1.00
52.89

276
CG
ASN
A
236
4.033
28.087
−15.799
1.00
52.48

277
OD1
ASN
A
236
3.453
29.148
−16.028
1.00
52.78

278
ND2
ASN
A
236
4.413
27.729
−14.580
1.00
52.90

279
C
ASN
A
236
6.701
28.005
−17.179
1.00
47.02

280
O
ASN
A
236
6.751
28.137
−15.956
1.00
47.14

281
N
PRO
A
237
7.783
28.170
−17.966
1.00
42.04

282
CD
PRO
A
237
7.651
28.434
−19.410
1.00
41.47

283
CA
PRO
A
237
9.145
28.475
−17.529
1.00
38.16

284
CD
PRO
A
237
9.906
28.523
−18.846
1.00
38.68

285
CG
PRO
A
237
8.920
29.198
−19.729
1.00
39.97

286
C
PRO
A
237
9.338
29.755
−16.740
1.00
34.87

287
O
PRO
A
237
8.615
30.734
−16.921
1.00
34.21

288
N
PRO
A
238
10.338
29.760
−15.848
1.00
32.12

289
CD
PRO
A
238
11.273
28.667
−15.531
1.00
32.31

290
CA
PRO
A
238
10.617
30.943
−15.038
1.00
29.30

291
CB
PRO
A
238
11.741
30.470
−14.114
1.00
29.79

292
CG
PRO
A
238
12.436
29.411
−14.933
1.00
32.45

293
C
PRO
A
238
11.045
32.080
−15.960
1.00
27.36

294
O
PRO
A
238
11.745
31.861
−16.952
1.00
25.06

295
N
PHE
A
239
10.606
33.289
−15.637
1.00
24.30

296
CA
PHE
A
239
10.939
34.458
−16.431
1.00
23.14

297
CB
PHE
A
239
10.004
35.612
−16.083
1.00
25.05

298
CG
PHE
A
239
10.111
36.768
−17.022
1.00
26.31

299
CD1
PHE
A
239
9.483
36.729
−18.262
1.00
27.99

300
CD2
PHE
A
239
10.874
37.881
−16.691
1.00
27.41

301
CE1
PHE
A
239
9.615
37.784
−19.162
1.00
28.47

302
CE2
PHE
A
239
11.014
38.940
−17.583
1.00
28.03

303
CZ
PHE
A
239
10.382
38.891
−18.823
1.00
29.16

304
C
PHE
A
239
12.370
34.872
−16.133
1.00
22.55

305
O
PHE
A
239
12.723
35.087
−14.976
1.00
19.83

306
N
VAL
A
240
13.189
35.002
−17.171
1.00
22.23

307
CA
VAL
A
240
14.581
35.377
−16.974
1.00
21.89

308
CB
VAL
A
240
15.492
34.735
−18.051
1.00
23.08

309
CG1
VAL
A
240
16.919
35.265
−17.916
1.00
22.71

310
CG2
VAL
A
240
15.487
33.217
−17.889
1.00
22.78

311
C
VAL
A
240
14.813
36.884
−16.959
1.00
22.84

312
O
VAL
A
240
14.387
37.613
−17.861
1.00
22.43

313
N
ILE
A
241
15.482
37.340
−15.905
1.00
20.77

314
CA
ILE
A
241
15.817
38.745
−15.740
1.00
20.91

315
CB
ILE
A
241
15.496
39.223
−14.306
1.00
20.98

316
CG2
ILE
A
241
15.897
40.687
−14.137
1.00
19.06

317
CG1
ILE
A
241
13.999
39.039
−14.028
1.00
19.24

318
CD1
ILE
A
241
13.607
39.288
−12.574
1.00
21.68

319
C
ILE
A
241
17.317
38.844
−16.006
1.00
21.63

320
O
ILE
A
241
18.137
38.438
−15.172
1.00
19.53

321
N
HIS
A
242
17.673
39.362
−17.181
1.00
20.99

322
CA
HIS
A
242
19.077
39.476
−17.568
1.00
22.26

323
CB
HIS
A
242
19.355
38.567
−18.769
1.00
24.28

324
CG
HIS
A
242
18.588
38.937
−19.998
1.00
24.97

325
CD2
HIS
A
242
17.459
38.415
−20.534
1.00
25.77

326
ND1
HIS
A
242
18.951
39.986
−20.816
1.00
27.65

327
CE1
HIS
A
242
18.077
40.096
−21.800
1.00
25.99

328
NE2
HIS
A
242
17.162
39.156
−21.653
1.00
26.18

329
C
HIS
A
242
19.537
40.902
−17.868
1.00
23.10

330
O
HIS
A
242
20.721
41.135
−18.111
1.00
21.51

331
N
ASP
A
243
18.600
41.847
−17.848
1.00
23.64

332
CA
ASP
A
243
18.910
43.255
−18.074
1.00
26.61

333
CB
ASP
A
243
19.170
43.546
−19.561
1.00
27.87

334
CG
ASP
A
243
17.972
43.258
−20.445
1.00
29.61

335
OD1
ASP
A
243
16.851
43.097
−19.921
1.00
28.47

336
OD2
ASP
A
243
18.157
43.206
−21.683
1.00
31.76

337
C
ASP
A
243
17.792
44.150
−17.553
1.00
27.23

338
O
ASP
A
243
16.800
43.668
−17.006
1.00
25.64

339
N
MET
A
244
17.953
45.457
−17.727
1.00
28.20

340
CA
MET
A
244
16.964
46.414
−17.243
1.00
28.88

341
CB
MET
A
244
17.466
47.838
−17.483
1.00
31.16

342
CG
MET
A
244
18.749
48.140
−16.733
1.00
33.46

343
SD
MET
A
244
18.511
48.081
−14.932
1.00
36.77

344
CE
MET
A
244
19.258
49.667
−14.476
1.00
37.18

345
C
MET
A
244
15.571
46.241
−17.837
1.00
28.34

346
O
MET
A
244
14.567
46.411
−17.138
1.00
27.10

347
N
GLU
A
245
15.500
45.895
−19.118
1.00
28.20

348
CA
GLU
A
245
14.206
45.709
−19.760
1.00
27.38

349
CB
GLU
A
245
14.375
45.546
−21.274
1.00
30.74

350
CG
GLU
A
245
13.072
45.246
−21.999
1.00
34.46

351
CD
GLU
A
245
13.226
45.229
−23.510
1.00
37.18

352
OE1
GLU
A
245
14.109
44.505
−24.016
1.00
38.99

353
OE2
GLU
A
245
12.455
45.936
−24.191
1.00
39.82

354
C
GLU
A
245
13.452
44.508
−19.189
1.00
26.77

355
O
GLU
A
245
12.274
44.615
−18.844
1.00
24.55

356
N
THR
A
246
14.126
43.366
−19.086
1.00
25.14

357
CA
THR
A
246
13.485
42.169
−18.550
1.00
22.92

358
CB
THR
A
246
14.342
40.909
−18.802
1.00
22.22

359
OG1
THR
A
246
15.686
41.135
−18.362
1.00
20.92

360
CG2
THR
A
246
14.352
40.571
−20.288
1.00
22.08

361
C
THR
A
246
13.172
42.299
−17.058
1.00
22.64

362
O
THR
A
246
12.284
41.615
−16.545
1.00
21.75

363
N
LEU
A
247
13.896
43.171
−16.360
1.00
21.77

364
CA
LEU
A
247
13.630
43.386
−14.936
1.00
20.25

365
CB
LEU
A
247
14.698
44.278
−14.289
1.00
20.20

366
CG
LEU
A
247
14.339
44.724
−12.861
1.00
18.26

367
CD1
LEU
A
247
14.285
43.498
−11.941
1.00
19.55

368
CD2
LEU
A
247
15.367
45.723
−12.342
1.00
17.68

369
C
LEU
A
247
12.280
44.081
−14.833
1.00
20.44

370
O
LEU
A
247
11.417
43.678
−14.064
1.00
19.24

371
N
CYS
A
248
12.094
45.126
−15.630
1.00
20.05

372
CA
CYS
A
248
10.833
45.856
−15.606
1.00
22.13

373
CB
CYS
A
248
10.904
47.076
−16.536
1.00
22.88

374
SG
CYS
A
248
12.090
48.355
−16.013
1.00
28.89

375
C
CYS
A
248
9.681
44.939
−16.016
1.00
22.46

376
O
CYS
A
248
8.594
45.020
−15.452
1.00
23.21

377
N
MET
A
249
9.921
44.067
−16.994
1.00
24.21

378
CA
MET
A
249
8.889
43.139
−17.465
1.00
25.70

379
CB
MET
A
249
9.392
42.333
−18.668
1.00
28.67

380
CG
MET
A
249
9.874
43.175
−19.847
1.00
34.04

381
SD
MET
A
249
10.480
42.192
−21.255
1.00
38.98

382
CE
MET
A
249
10.112
43.318
−22.621
1.00
38.27

383
C
MET
A
249
8.504
42.178
−16.342
1.00
25.87

384
O
MET
A
249
7.323
41.924
−16.098
1.00
25.43

385
N
ALA
A
250
9.511
41.646
−15.657
1.00
24.88

386
CA
ALA
A
250
9.268
40.720
−14.559
1.00
23.76

387
CB
ALA
A
250
10.590
40.188
−14.022
1.00
22.98

388
C
ALA
A
250
8.482
41.406
−13.446
1.00
22.99

389
O
ALA
A
250
7.546
40.829
−12.889
1.00
23.42

390
N
GLU
A
251
8.863
42.639
−13.121
1.00
22.90

391
CA
GLU
A
251
8.176
43.387
−12.075
1.00
23.30

392
CB
GLU
A
251
8.840
44.756
−11.865
1.00
23.04

393
CG
GLU
A
251
10.269
44.676
−11.336
1.00
23.77

394
CD
GLU
A
251
10.969
46.025
−11.283
1.00
25.32

395
OE1
GLU
A
251
10.914
46.766
−12.288
1.00
26.09

396
OE2
GLU
A
251
11.590
46.341
−10.247
1.00
24.65

397
C
GLU
A
251
6.713
43.572
−12.465
1.00
24.60

398
O
GLU
A
251
5.815
43.401
−11.646
1.00
23.99

399
N
LYS
A
252
6.482
43.911
−13.728
1.00
26.88

400
CA
LYS
A
252
5.129
44.120
−14.227
1.00
29.38

401
CB
LYS
A
252
5.163
44.406
−15.729
1.00
31.11

402
CG
LYS
A
252
3.792
44.688
−16.321
1.00
34.55

403
CD
LYS
A
252
3.707
46.086
−16.917
1.00
38.59

404
CE
LYS
A
252
4.142
47.146
−15.921
1.00
40.59

405
NZ
LYS
A
252
5.625
47.202
−15.814
1.00
42.89

406
C
LYS
A
252
4.229
42.912
−13.965
1.00
30.43

407
O
LYS
A
252
3.045
43.059
−13.656
1.00
30.61

408
N
THR
A
253
4.797
41.717
−14.083
1.00
31.64

409
CA
THR
A
253
4.035
40.492
−13.879
1.00
32.66

410
CB
THR
A
253
4.508
39.385
−14.840
1.00
34.32

411
OG1
THR
A
253
4.522
39.884
−16.185
1.00
37.49

412
CG2
THR
A
253
3.564
38.191
−14.767
1.00
34.76

413
C
THR
A
253
4.076
39.923
−12.459
1.00
32.57

414
O
THR
A
253
3.033
39.621
−11.876
1.00
33.27

415
N
LEU
A
254
5.275
39.784
−11.904
1.00
31.54

416
CA
LEU
A
254
5.441
39.208
−10.572
1.00
31.84

417
CB
LEU
A
254
6.805
38.522
−10.489
1.00
32.07

418
CG
LEU
A
254
6.933
37.131
−11.126
1.00
33.07

419
CD1
LEU
A
254
5.781
36.849
−12.083
1.00
32.88

420
CD2
LEU
A
254
8.271
37.040
−11.833
1.00
32.53

421
C
LEU
A
254
5.256
40.128
−9.367
1.00
32.52

422
O
LEU
A
254
4.770
39.690
−8.321
1.00
31.50

423
N
VAL
A
255
5.654
41.389
−9.501
1.00
32.08

424
CA
VAL
A
255
5.514
42.353
−8.413
1.00
32.49

425
CB
VAL
A
255
6.870
42.614
−7.710
1.00
32.30

426
CG1
VAL
A
255
6.698
43.659
−6.620
1.00
33.97

427
CG2
VAL
A
255
7.393
41.322
−7.095
1.00
33.63

428
C
VAL
A
255
4.988
43.650
−9.017
1.00
33.56

429
O
VAL
A
255
5.664
44.680
−9.018
1.00
32.17

430
N
ALA
A
256
3.766
43.571
−9.532
1.00
34.97

431
CA
ALA
A
256
3.092
44.685
−10.192
1.00
35.76

432
CB
ALA
A
256
1.636
44.310
−10.438
1.00
37.47

433
C
ALA
A
256
3.162
46.065
−9.529
1.00
37.14

434
O
ALA
A
256
3.127
47.083
−10.224
1.00
35.98

435
N
LYS
A
257
3.267
46.114
−8.203
1.00
37.87

436
CA
LYS
A
257
3.310
47.404
−7.509
1.00
39.85

437
CB
LYS
A
257
3.154
47.210
−5.995
1.00
39.30

438
GG
LYS
A
257
3.135
48.531
−5.218
1.00
40.41

439
CD
LYS
A
257
3.092
48.326
−3.708
1.00
41.21

440
CE
LYS
A
257
1.717
47.890
−3.228
1.00
42.93

441
NZ
LYS
A
257
0.674
48.923
−3.504
1.00
44.25

442
C
LYS
A
257
4.553
48.260
−7.772
1.00
40.87

443
O
LYS
A
257
4.477
49.489
−7.764
1.00
41.16

444
N
LEU
A
258
5.693
47.618
−7.999
1.00
41.92

445
CA
LEU
A
258
6.934
48.347
−8.241
1.00
43.90

446
CB
LEU
A
258
8.133
47.431
−8.002
1.00
43.36

447
CG
LEU
A
258
8.106
46.627
−6.702
1.00
42.94

448
CD1
LEU
A
258
9.465
45.980
−6.481
1.00
42.92

449
CD2
LEU
A
258
7.756
47.541
−5.536
1.00
43.54

450
C
LEU
A
258
7.021
48.917
−9.647
1.00
45.44

451
O
LEU
A
258
8.118
49.189
−10.142
1.00
45.30

452
N
VAL
A
259
5.874
49.138
−10.277
1.00
47.08

453
CA
VAL
A
259
5.899
49.643
−11.634
1.00
49.10

454
CB
VAL
A
259
5.984
48.463
−12.612
1.00
49.12

455
CG1
VAL
A
259
4.606
47.839
−12.800
1.00
49.41

456
CG2
VAL
A
259
6.587
48.926
−13.921
1.00
49.20

457
C
VAL
A
259
4.716
50.538
−12.012
1.00
50.30

458
O
VAL
A
259
4.459
50.771
−13.194
1.00
50.13

459
N
ALA
A
260
4.010
51.065
−11.016
1.00
51.85

460
CA
ALA
A
260
2.860
51.925
−11.304
1.00
53.91

461
CB
ALA
A
260
1.627
51.065
−11.582
1.00
53.84

462
C
ALA
A
260
2.542
52.938
−10.207
1.00
55.04

463
O
ALA
A
260
1.443
53.496
−10.173
1.00
55.68

464
N
ASN
A
261
3.496
53.182
−9.314
1.00
55.70

465
CA
ASN
A
261
3.277
54.134
−8.225
1.00
57.57

466
CB
ASN
A
261
3.064
53.389
−6.905
1.00
20.38

467
CG
ASN
A
261
1.795
52.578
−6.902
1.00
20.38

468
OD1
ASN
A
261
1.812
51.370
−7.162
1.00
20.38

469
ND2
ASN
A
261
0.670
53.245
−6.633
1.00
20.38

470
C
ASN
A
261
4.414
55.132
−8.048
1.00
58.36

471
O
ASN
A
261
4.672
55.595
−6.937
1.00
58.74

472
N
GLY
A
262
5.081
55.473
−9.145
1.00
20.38

473
CA
GLY
A
262
6.204
56.394
−9.063
1.00
20.38

474
C
GLY
A
262
7.442
55.570
−8.751
1.00
20.38

475
O
GLY
A
262
8.576
56.039
−8.883
1.00
20.38

476
N
ILE
A
263
7.213
54.319
−8.352
1.00
58.34

477
CA
ILE
A
263
8.300
53.404
−8.015
1.00
57.76

478
CB
ILE
A
263
7.787
52.149
−7.293
1.00
58.40

479
CG2
ILE
A
263
8.946
51.405
−6.661
1.00
58.51

480
CG1
ILE
A
263
6.764
52.524
−6.225
1.00
58.87

481
CD1
ILE
A
263
6.170
51.325
−5.498
1.00
59.43

482
C
ILE
A
263
9.054
52.942
−9.254
1.00
57.27

483
O
ILE
A
263
10.193
52.497
−9.157
1.00
57.93

484
N
GLN
A
264
8.410
53.027
−10.415
1.00
55.75

485
CA
GLN
A
264
9.038
52.596
−11.658
1.00
54.43

486
CB
GLN
A
264
8.116
52.845
−12.849
1.00
54.62

487
CG
GLN
A
264
7.654
54.270
−13.006
1.00
54.62

488
CD
GLN
A
264
6.221
54.465
−12.572
1.00
54.37

489
OE1
GLN
A
264
5.896
54.391
−11.390
1.00
54.65

490
NB2
GLN
A
264
5.347
54.710
−13.539
1.00
53.99

491
C
GLN
A
264
10.378
53.265
−11.896
1.00
53.23

492
O
GLN
A
264
11.164
52.791
−12.714
1.00
53.33

493
N
ASN
A
265
10.648
54.369
−11.203
1.00
51.79

494
CA
ASN
A
265
11.943
54.991
−11.390
1.00
50.16

495
CB
ASN
A
265
11.889
56.162
−12.357
1.00
52.29

496
CG
ASN
A
265
13.036
56.120
−13.366
1.00
54.63

497
OD1
ASN
A
265
13.488
57.150
−13.866
1.00
56.51

498
ND2
ASN
A
265
13.504
54.914
−13.673
1.00
55.84

499
C
ASN
A
265
12.728
55.397
−10.164
1.00
47.37

500
O
ASN
A
265
13.251
56.509
−10.078
1.00
47.22

501
N
LYS
A
266
12.765
54.494
−9.195
1.00
43.69

502
CA
LYS
A
266
13.617
54.669
−8.039
1.00
38.70

503
CB
LYS
A
266
13.077
53.921
−6.817
1.00
39.95

504
CG
LYS
A
266
11.973
54.657
−6.077
1.00
41.04

505
CD
LYS
A
266
11.700
54.020
−4.721
1.00
42.78

506
CE
LYS
A
266
10.676
54.817
−3.920
1.00
43.67

507
NZ
LYS
A
266
10.422
54.216
−2.578
1.00
44.37

508
C
LYS
A
266
14.628
53.824
−8.797
1.00
35.85

509
O
LYS
A
266
14.207
52.956
−9.570
1.00
32.72

510
N
GLU
A
267
15.926
54.045
−8.653
1.00
33.11

511
CA
GLU
A
267
16.809
53.225
−9.468
1.00
30.98

512
CB
GLU
A
267
18.281
53.630
−9.312
1.00
34.18

513
CG
GLU
A
267
18.846
53.674
−7.923
1.00
36.39

514
CD
GLU
A
267
20.153
54.445
−7.890
1.00
36.02

515
OE1
GLU
A
267
21.030
54.183
−8.740
1.00
36.54

516
OE2
GLU
A
267
20.305
55.317
−7.014
1.00
38.61

517
C
GLU
A
267
16.604
51.732
−9.252
1.00
29.49

518
O
GLU
A
267
16.183
51.288
−8.184
1.00
26.80

519
N
ALA
A
268
16.868
50.970
−10.306
1.00
26.80

520
CA
ALA
A
268
16.702
49.526
−10.293
1.00
27.28

521
CB
ALA
A
268
17.312
48.937
−11.549
1.00
26.70

522
C
ALA
A
268
17.280
48.838
−9.064
1.00
24.93

523
O
ALA
A
268
16.620
47.991
−8.459
1.00
23.64

524
N
GLU
A
269
18.504
49.199
−8.685
1.00
22.59

525
CA
GLU
A
269
19.126
48.561
−7.536
1.00
22.23

526
CB
GLU
A
269
20.539
49.116
−7.274
1.00
23.67

527
CG
GLU
A
269
20.876
50.450
−7.915
1.00
27.55

528
CD
GLU
A
269
21.024
50.367
−9.423
1.00
24.59

529
OE1
GLU
A
269
20.048
50.679
−10.116
1.00
26.10

530
OE2
GLU
A
269
22.109
49.985
−9.918
1.00
26.97

531
C
GLU
A
269
18.291
48.654
−6.263
1.00
22.57

532
O
GLU
A
269
18.307
47.737
−5.447
1.00
21.72

533
N
VAL
A
270
17.553
49.746
−6.095
1.00
21.59

534
CA
VAL
A
270
16.728
49.911
−4.899
1.00
21.26

535
CB
VAL
A
270
16.290
51.377
−4.730
1.00
23.06

536
CG1
VAL
A
270
15.279
51.504
−3.604
1.00
25.08

537
CG2
VAL
A
270
17.509
52.238
−4.430
1.00
25.52

538
C
VAL
A
270
15.502
49.001
−4.950
1.00
19.49

539
O
VAL
A
270
15.064
48.468
−3.921
1.00
18.78

540
N
ARG
A
271
14.956
48.820
−6.149
1.00
18.65

541
CA
ARG
A
271
13.799
47.948
−6.340
1.00
17.90

542
CB
ARG
A
271
13.238
48.104
−7.760
1.00
18.81

543
CG
ARG
A
271
12.207
49.209
−7.891
1.00
23.01

544
CD
ARG
A
271
12.325
49.944
−9.206
1.00
23.63

545
NE
ARG
A
271
12.388
49.055
−10.366
1.00
21.82

546
CZ
ARG
A
271
12.893
49.422
−11.539
1.00
23.69

547
NH1
ARG
A
271
13.374
50.649
−11.693
1.00
25.06

548
NH2
ARG
A
271
12.923
48.573
−12.554
1.00
24.09

549
C
ARG
A
271
14.219
46.498
−6.102
1.00
17.66

550
O
ARG
A
271
13.528
45.743
−5.420
1.00
16.97

551
N
ILE
A
272
15.361
46.118
−6.662
1.00
17.24

552
CA
ILE
A
272
15.879
44.762
−6.499
1.00
16.58

553
CB
ILE
A
272
17.151
44.558
−7.346
1.00
17.41

554
CG2
ILE
A
272
17.842
43.238
−6.962
1.00
17.49

555
CG1
ILE
A
272
16.772
44.568
−8.832
1.00
17.66

556
CD1
ILE
A
272
17.954
44.508
−9.785
1.00
19.17

557
C
ILE
A
272
16.193
44.505
−5.026
1.00
16.90

558
O
ILE
A
272
15.893
43.434
−4.499
1.00
16.85

559
N
PHE
A
273
16.779
45.497
−4.361
1.00
14.57

560
CA
PHE
A
273
17.114
45.364
−2.943
1.00
13.82

561
CB
PHE
A
273
17.884
46.591
−2.456
1.00
14.33

562
CG
PHE
A
273
18.485
46.427
−1.086
1.00
16.86

563
CD1
PHE
A
273
19.604
45.626
−0.899
1.00
17.16

564
CD2
PHE
A
273
17.937
47.078
0.012
1.00
16.21

565
CE1
PHE
A
273
20.174
45.475
0.356
1.00
18.94

566
CE2
PHE
A
273
18.498
46.936
1.275
1.00
19.15

567
CZ
PHE
A
273
19.621
46.133
1.448
1.00
20.18

568
C
PHE
A
273
15.850
45.203
−2.102
1.00
14.30

569
O
PHE
A
273
15.860
44.505
−1.096
1.00
15.47

570
N
HIS
A
274
14.768
45.874
−2.496
1.00
14.52

571
CA
HIS
A
274
13.519
45.756
−1.758
1.00
15.32

572
CB
HIS
A
274
12.455
46.695
−2.330
1.00
16.74

573
CG
HIS
A
274
11.139
46.603
−1.624
1.00
18.93

574
CD2
HIS
A
274
9.960
46.057
−2.003
1.00
21.47

575
ND1
HIS
A
274
10.954
47.061
−0.337
1.00
19.40

576
CE1
HIS
A
274
9.718
46.799
0.047
1.00
21.96

577
NE2
HIS
A
274
9.093
46.189
−0.945
1.00
23.33

578
C
HIS
A
274
13.033
44.312
−1.878
1.00
14.53

579
O
HIS
A
274
12.605
43.706
−0.903
1.00
15.83

580
N
CYS
A
275
13.096
43.769
−3.088
1.00
14.60

581
CA
CYS
A
275
12.674
42.388
−3.323
1.00
14.94

582
CB
CYS
A
275
12.721
42.064
−4.816
1.00
14.09

583
SG
CYS
A
275
11.470
42.950
−5.767
1.00
16.01

584
C
CYS
A
275
13.558
41.414
−2.544
1.00
14.97

585
O
CYS
A
275
13.090
40.366
−2.099
1.00
13.78

586
N
CYS
A
276
14.836
41.748
−2.383
1.00
15.23

587
CA
CYS
A
276
15.740
40.880
−1.625
1.00
13.47

588
CB
CYS
A
276
17.180
41.409
−1.667
1.00
15.89

589
SG
CYS
A
276
17.996
41.235
−3.256
1.00
15.55

590
C
CYS
A
276
15.265
40.844
−0.176
1.00
15.09

591
O
CYS
A
276
15.264
39.789
0.467
1.00
15.43

592
N
GLN
A
277
14.861
42.005
0.332
1.00
13.05

593
CA
GLN
A
277
14.379
42.105
1.707
1.00
14.74

594
CB
GLN
A
277
14.150
43.564
2.100
1.00
16.57

595
CG
GLN
A
277
15.418
44.386
2.205
1.00
18.11

596
CD
GLN
A
277
15.231
45.597
3.093
1.00
20.26

597
OE1
GLN
A
277
14.949
45.465
4.286
1.00
22.83

598
NE2
GLN
A
277
15.383
46.784
2.520
1.00
22.10

599
C
GLN
A
277
13.086
41.339
1.909
1.00
14.38

600
O
GLN
A
277
12.905
40.665
2.924
1.00
14.08

601
N
CYS
A
278
12.175
41.451
0.949
1.00
14.67

602
CA
CYS
A
278
10.911
40.741
1.062
1.00
15.04

603
CB
CYS
A
278
9.994
41.091
−0.110
1.00
16.30

604
SG
CYS
A
278
9.396
42.797
−0.061
1.00
22.25

605
C
CYS
A
278
11.192
39.245
1.093
1.00
14.70

606
O
CYS
A
278
10.593
38.505
1.868
1.00
14.34

607
N
THR
A
279
12.119
38.813
0.244
1.00
14.73

608
CA
THR
A
279
12.517
37.412
0.164
1.00
14.32

609
CB
THR
A
279
13.514
37.211
−0.997
1.00
15.37

610
OG1
THR
A
279
12.888
37.603
−2.230
1.00
13.87

611
GG2
THR
A
279
13.943
35.748
−1.094
1.00
14.11

612
C
THR
A
279
13.135
36.946
1.488
1.00
14.08

613
O
THR
A
279
12.771
35.897
2.029
1.00
13.41

614
N
SER
A
280
14.057
37.732
2.028
1.00
12.61

615
CA
SER
A
280
14.672
37.371
3.303
1.00
12.61

616
CB
SER
A
280
15.775
38.361
3.657
1.00
12.19

617
OG
SER
A
280
16.915
38.120
2.860
1.00
11.40

618
C
SER
A
280
13.660
37.309
4.450
1.00
12.67

619
O
SER
A
280
13.726
36.413
5.283
1.00
12.90

620
N
VAL
A
281
12.720
38.249
4.492
1.00
13.57

621
CA
VAL
A
281
11.723
38.249
5.563
1.00
13.84

622
CB
VAL
A
281
10.790
39.480
5.461
1.00
15.55

623
CG1
VAL
A
281
9.555
39.303
6.345
1.00
17.55

624
CG2
VAL
A
281
11.558
40.721
5.895
1.00
16.53

625
C
VAL
A
281
10.911
36.961
5.533
1.00
15.35

626
O
VAL
A
281
10.639
36.366
6.575
1.00
14.98

627
N
GLU
A
282
10.546
36.522
4.334
1.00
16.73

628
CA
GLU
A
282
9.777
35.292
4.182
1.00
16.47

629
CB
GLU
A
282
9.338
35.113
2.726
1.00
19.03

630
GG
GLU
A
282
8.344
36.159
2.235
1.00
22.45

631
CD
GLU
A
282
6.924
35.908
2.727
1.00
27.72

632
OE1
GLU
A
282
6.724
34.990
3.558
1.00
28.03

633
OE2
GLU
A
282
6.009
36.635
2.279
1.00
27.23

634
C
GLU
A
282
10.603
34.088
4.612
1.00
15.29

635
O
GLU
A
282
10.099
33.192
5.282
1.00
14.93

636
N
THR
A
283
11.877
34.066
4.235
1.00
13.72

637
CA
THR
A
283
12.727
32.937
4.590
1.00
13.42

638
CB
THR
A
283
14.070
33.003
3.843
1.00
13.57

639
OG1
THR
A
283
13.822
33.115
2.433
1.00
13.65

640
CG2
THR
A
283
14.878
31.738
4.091
1.00
13.97

641
C
THR
A
283
12.961
32.876
6.097
1.00
13.92

642
O
THR
A
283
12.956
31.796
6.687
1.00
15.10

643
N
VAL
A
284
13.159
34.034
6.723
1.00
14.12

644
CA
VAL
A
284
13.359
34.074
8.176
1.00
14.58

645
CB
VAL
A
284
13.612
35.508
8.674
1.00
14.45

646
001
VAL
A
284
13.507
35.559
10.200
1.00
15.36

647
CG2
VAL
A
284
14.976
35.980
8.225
1.00
15.78

648
C
VAL
A
284
12.097
33.541
8.861
1.00
14.26

649
O
VAL
A
284
12.165
32.827
9.870
1.00
14.04

650
N
THR
A
285
10.944
33.900
8.309
1.00
15.03

651
CA
THR
A
285
9.670
33.458
8.866
1.00
16.55

652
CB
THR
A
285
8.493
34.139
8.133
1.00
17.70

653
OG1
THR
A
285
8.641
35.566
8.224
1.00
18.26

654
CG2
THR
A
285
7.160
33.743
8.759
1.00
18.59

655
C
THR
A
285
9.551
31.931
8.775
1.00
16.67

656
O
THR
A
285
9.108
31.279
9.719
1.00
15.85

657
N
GLU
A
286
9.959
31.354
7.648
1.00
16.45

658
CA
GLU
A
286
9.897
29.897
7.489
1.00
14.59

659
CB
GLU
A
286
10.199
29.492
6.040
1.00
17.05

660
CG
GLU
A
286
9.201
29.983
5.025
1.00
19.53

661
CD
GLU
A
286
9.539
29.509
3.621
1.00
21.27

662
OE1
GLU
A
286
10.740
29.424
3.291
1.00
24.29

663
OE2
GLU
A
286
8.606
29.235
2.846
1.00
26.60

664
C
GLU
A
286
10.894
29.184
8.410
1.00
15.53

665
O
GLU
A
286
10.598
28.121
8.964
1.00
14.95

666
N
LEU
A
287
12.080
29.767
8.559
1.00
14.15

667
CA
LEU
A
287
13.117
29.183
9.404
1.00
14.54

668
CB
LEU
A
287
14.418
29.977
9.244
1.00
13.35

669
CG
LEU
A
287
15.286
29.532
8.062
1.00
13.79

670
CD1
LEU
A
287
16.277
30.630
7.670
1.00
14.77

671
CD2
LEU
A
287
16.029
28.253
8.452
1.00
15.41

672
C
LEU
A
287
12.684
29.185
10.863
1.00
15.65

673
O
LEU
A
287
13.017
28.277
11.627
1.00
15.76

674
N
THR
A
288
11.946
30.219
11.245
1.00
16.74

675
CA
THR
A
288
11.468
30.342
12.616
1.00
17.31

676
CB
THR
A
288
10.814
31.724
12.830
1.00
17.24

677
OG1
THR
A
288
11.821
32.736
12.693
1.00
18.00

678
CG2
THR
A
288
10.180
31.832
14.221
1.00
18.26

679
C
THR
A
288
10.484
29.211
12.913
1.00
18.94

680
O
THR
A
288
10.520
28.615
13.995
1.00
18.36

681
N
GLU
A
289
9.617
28.906
11.947
1.00
18.64

682
CA
GLU
A
289
8.654
27.824
12.120
1.00
19.64

683
CB
GLU
A
289
7.591
27.868
11.019
1.00
20.78

684
CG
GLU
A
289
6.701
29.088
11.102
1.00
24.51

685
CD
GLU
A
289
5.978
29.170
12.429
1.00
27.16

686
OE1
GLU
A
289
5.151
28.276
12.705
1.00
28.65

687
OE2
GLU
A
289
6.245
30.118
13.197
1.00
29.29

688
C
GLU
A
289
9.378
26.482
12.094
1.00
19.12

689
O
GLU
A
289
8.998
25.550
12.802
1.00
19.43

690
N
PHE
A
290
10.414
26.381
11.263
1.00
18.63

691
CA
PHE
A
290
11.215
25.158
11.177
1.00
18.56

692
CB
PHE
A
290
12.295
25.304
10.097
1.00
18.22

693
CG
PHE
A
290
13.295
24.178
10.074
1.00
16.52

694
CD1
PHE
A
290
12.913
22.894
9.702
1.00
15.73

695
CD2
PHE
A
290
14.628
24.411
10.407
1.00
16.62

696
CE1
PHE
A
290
13.844
21.854
9.657
1.00
16.62

697
CE2
PHE
A
290
15.564
23.387
10.367
1.00
16.63

698
CZ
PHE
A
290
15.170
22.097
9.987
1.00
16.10

699
C
PHE
A
290
11.894
24.898
12.525
1.00
19.02

700
O
PHE
A
290
11.856
23.783
13.049
1.00
19.20

701
N
ALA
A
291
12.529
25.931
13.073
1.00
19.85

702
CA
ALA
A
291
13.226
25.800
14.353
1.00
19.89

703
CB
ALA
A
291
13.856
27.130
14.746
1.00
20.05

704
C
ALA
A
291
12.270
25.337
15.449
1.00
21.19

705
O
A1A
A
291
12.623
24.499
16.283
1.00
19.62

706
N
LYS
A
292
11.064
25.897
15.447
1.00
21.75

707
CA
LYS
A
292
10.053
25.545
16.439
1.00
23.62

708
CB
LYS
A
292
8.802
26.407
16.245
1.00
22.82

709
CG
LYS
A
292
8.959
27.846
16.715
1.00
27.26

710
CD
LYS
A
292
7.821
28.738
16.214
1.00
30.13

711
CE
LYS
A
292
6.452
28.165
16.544
1.00
32.35

712
NZ
LYS
A
292
6.234
28.014
18.007
1.00
36.87

713
C
LYS
A
292
9.686
24.070
16.346
1.00
24.64

714
O
LYS
A
292
9.150
23.493
17.295
1.00
24.87

715
N
ALA
A
293
9.983
23.460
15.202
1.00
24.73

716
CA
ALA
A
293
9.684
22.051
14.985
1.00
24.93

717
CB
ALA
A
293
9.190
21.840
13.562
1.00
24.81

718
C
ALA
A
293
10.871
21.129
15.274
1.00
24.71

719
O
ALA
A
293
10.750
19.909
15.185
1.00
23.86

720
N
ILE
A
294
12.024
21.704
15.606
1.00
23.98

721
CA
ILE
A
294
13.188
20.885
15.925
1.00
22.06

722
CB
ILE
A
294
14.511
21.661
15.764
1.00
21.52

723
CG2
ILE
A
294
15.684
20.769
16.166
1.00
20.29

724
CG1
ILE
A
294
14.687
22.112
14.310
1.00
18.78

725
CDI
ILE
A
294
15.938
22.940
14.085
1.00
20.43

726
C
ILE
A
294
13.065
20.448
17.383
1.00
23.55

727
O
ILE
A
294
13.023
21.284
18.284
1.00
22.86

728
N
PRO
A
295
13.006
19.130
17.629
1.00
24.07

729
CD
PRO
A
295
13.131
18.036
16.648
1.00
23.94

730
CA
PRO
A
295
12.885
18.592
18.989
1.00
24.71

731
CB
PRO
A
295
13.284
17.135
18.808
1.00
24.70

732
CG
PRO
A
295
12.728
16.824
17.458
1.00
25.44

733
C
PRO
A
295
13.757
19.301
20.023
1.00
24.62

734
O
PRO
A
295
14.985
19.321
19.906
1.00
25.02

735
N
GLY
A
296
13.114
19.889
21.029
1.00
23.49

736
CA
GLY
A
296
13.854
20.563
22.081
1.00
23.80

737
C
GLY
A
296
14.022
22.064
21.948
1.00
22.79

738
O
GLY
A
296
14.240
22.752
22.948
1.00
21.27

739
N
PHE
A
297
13.928
22.583
20.728
1.00
22.01

740
CA
PHE
A
297
14.097
24.019
20.518
1.00
22.24

741
CB
PHE
A
297
14.011
24.358
19.025
1.00
21.13

742
CG
PHE
A
297
14.296
25.805
18.715
1.00
20.73

743
CD1
PHE
A
297
13.287
26.760
18.780
1.00
21.28

744
CD2
PHE
A
297
15.584
26.215
18.389
1.00
20.25

745
CE1
PHE
A
297
13.560
28.105
18.523
1.00
20.90

746
CE2
PHE
A
297
15.867
27.556
18.131
1.00
19.14

747
CZ
PHE
A
297
14.856
28.500
18.199
1.00
19.75

748
C
PHE
A
297
13.080
24.854
21.289
1.00
22.26

749
O
PHE
A
297
13.439
25.835
21.945
1.00
22.51

750
N
ALA
A
298
11.813
24.464
21.217
1.00
23.86

751
CA
ALA
A
298
10.754
25.206
21.896
1.00
24.65

752
CB
ALA
A
298
9.391
24.693
21.450
1.00
25.58

753
C
ALA
A
298
10.862
25.154
23.418
1.00
25.96

754
O
ALA
A
298
10.229
25.947
24.111
1.00
26.50

755
N
ASN
A
299
11.668
24.230
23.933
1.00
26.32

756
CA
ASN
A
299
11.856
24.088
25.377
1.00
26.91

757
CB
ASN
A
299
12.296
22.663
25.714
1.00
27.32

758
CG
ASN
A
299
11.198
21.648
25.496
1.00
27.93

759
OD1
ASN
A
299
11.456
20.447
25.428
1.00
31.25

760
ND2
ASN
A
299
9.962
22.123
25.393
1.00
27.97

761
C
ASN
A
299
12.891
25.068
25.923
1.00
27.12

762
O
ASN
A
299
12.982
25.288
27.134
1.00
26.42

763
N
LEU
A
300
13.684
25.642
25.028
1.00
24.59

764
CA
LEU
A
300
14.705
26.596
25.433
1.00
23.00

765
CB
LEU
A
300
15.620
26.921
24.252
1.00
20.53

766
CG
LEU
A
300
16.484
25.795
23.687
1.00
20.80

767
CD1
LEU
A
300
17.176
26.283
22.424
1.00
20.69

768
CD2
LEU
A
300
17.509
25.357
24.729
1.00
21.60

769
C
LEU
A
300
14.046
27.873
25.909
1.00
21.59

770
O
LEU
A
300
12.900
28.141
25.571
1.00
20.49

771
N
ASP
A
301
14.771
28.654
26.703
1.00
23.45

772
CA
ASP
A
301
14.252
29.931
27.172
1.00
23.40

773
CB
ASP
A
301
15.276
30.636
28.058
1.00
22.34

774
CG
ASP
A
301
14.863
32.052
28.406
1.00
23.70

775
OD1
ASP
A
301
13.868
32.225
29.135
1.00
24.73

776
OD2
ASP
A
301
15.531
33.000
27.941
1.00
24.97

777
C
ASP
A
301
14.049
30.738
25.894
1.00
23.49

778
O
ASP
A
301
14.817
30.584
24.945
1.00
22.64

779
N
LEU
A
302
13.029
31.588
25.863
1.00
24.03

780
CA
LEU
A
302
12.760
32.376
24.665
1.00
24.61

781
CB
LEU
A
302
11.486
33.209
24.845
1.00
25.91

782
CG
LEU
A
302
11.303
34.143
26.039
1.00
29.90

783
CD1
LEU
A
302
12.353
35.243
26.046
1.00
31.19

784
CD2
LEU
A
302
9.910
34.751
25.944
1.00
32.22

785
C
LEU
A
302
13.914
33.274
24.222
1.00
23.78

786
O
LEU
A
302
14.078
33.525
23.031
1.00
22.46

787
N
ASN
A
303
14.710
33.764
25.168
1.00
22.87

788
CA
ASN
A
303
15.842
34.615
24.814
1.00
23.57

789
CB
ASN
A
303
16.499
35.183
26.072
1.00
24.41

790
OG
ASN
A
303
15.597
36.151
26.812
1.00
25.82

791
OD1
ASN
A
303
15.341
37.265
26.346
1.00
24.76

792
ND2
ASN
A
303
15.097
35.724
27.969
1.00
25.85

793
C
ASN
A
303
16.858
33.792
24.025
1.00
23.03

794
O
ASN
A
303
17.475
34.279
23.071
1.00
22.95

795
N
ASP
A
304
17.031
32.539
24.428
1.00
21.92

796
CA
ASP
A
304
17.965
31.659
23.742
1.00
21.37

797
CB
ASP
A
304
18.232
30.404
24.570
1.00
20.90

798
CG
ASP
A
304
19.282
30.630
25.640
1.00
20.90

799
OD1
ASP
A
304
19.790
31.766
25.753
1.00
22.16

800
OD2
ASP
A
304
19.602
29.671
26.365
1.00
22.62

801
C
ASP
A
304
17.414
31.284
22.375
1.00
20.42

802
O
ASP
A
304
18.177
31.074
21.433
1.00
21.27

803
N
GLN
A
305
16.091
31.200
22.264
1.00
19.98

804
CA
GLN
A
305
15.478
30.871
20.978
1.00
20.73

805
CB
GLN
A
305
13.969
30.644
21.124
1.00
20.41

806
CG
GLN
A
305
13.593
29.369
21.870
1.00
22.80

807
CD
GLN
A
305
12.093
29.135
21.911
1.00
24.47

808
OE1
GLN
A
305
11.420
29.157
20.880
1.00
26.99

809
NE2
GLN
A
305
11.562
28.903
23.107
1.00
23.97

810
C
GLN
A
305
15.738
32.036
20.027
1.00
19.47

811
O
GLN
A
305
16.093
31.838
18.865
1.00
19.20

812
N
VAL
A
306
15.561
33.250
20.539
1.00
19.92

813
CA
VAL
A
306
15.787
34.463
19.760
1.00
18.92

814
CB
VAL
A
306
15.414
35.717
20.582
1.00
19.64

815
CG1
VAL
A
306
15.853
36.982
19.860
1.00
20.62

816
CG2
VAL
A
306
13.912
35.747
20.802
1.00
19.50

817
C
VAL
A
306
17.246
34.559
19.321
1.00
18.13

818
O
VAL
A
306
17.539
34.860
18.160
1.00
17.71

819
N
THR
A
307
18.159
34.293
20.250
1.00
17.09

820
CA
THR
A
307
19.586
34.361
19.957
1.00
17.05

821
CB
THR
A
307
20.424
34.138
21.242
1.00
17.63

822
OG1
THR
A
307
20.153
35.197
22.171
1.00
16.06

823
CG2
THR
A
307
21.918
34.135
20.921
1.00
16.45

824
C
THR
A
307
20.006
33.346
18.892
1.00
16.61

825
O
THR
A
307
20.766
33.672
17.986
1.00
17.34

826
N
LEU
A
308
19.503
32.121
18.994
1.00
15.88

827
CA
LEU
A
308
19.865
31.093
18.025
1.00
16.20

828
CB
LEU
A
308
19.262
29.741
18.417
1.00
17.78

829
CG
LEU
A
308
19.884
29.111
19.664
1.00
16.63

830
CD1
LEU
A
308
19.285
27.720
19.912
1.00
17.89

831
CD2
LEU
A
308
21.393
29.016
19.472
1.00
17.96

832
C
LEU
A
308
19.422
31.479
16.622
1.00
16.44

833
O
LEU
A
308
20.154
31.263
15.650
1.00
17.08

834
N
LEU
A
309
18.224
32.043
16.511
1.00
16.59

835
CA
LEU
A
309
17.724
32.463
15.204
1.00
17.03

836
CB
LEU
A
309
16.211
32.710
15.261
1.00
16.97

837
CG
LEU
A
309
15.373
31.426
15.326
1.00
18.35

838
CD1
LEU
A
309
13.914
31.777
15.589
1.00
23.00

839
CD2
LEU
A
309
15.506
30.657
14.020
1.00
19.92

840
C
LEU
A
309
18.447
33.726
14.751
1.00
17.00

841
O
LEU
A
309
18.825
33.855
13.587
1.00
17.06

842
N
LYS
A
310
18.649
34.657
15.675
1.00
16.85

843
CA
LYS
A
310
19.332
35.903
15.336
1.00
17.88

844
CB
LYS
A
310
19.570
36.737
16.595
1.00
19.60

845
CG
LYS
A
310
20.250
38.079
16.325
1.00
21.39

846
CD
LYS
A
310
20.640
38.760
17.633
1.00
24.10

847
CE
LYS
A
310
21.273
40.120
17.385
1.00
24.44

848
NZ
LYS
A
310
20.305
41.066
16.750
1.00
26.22

849
C
LYS
A
310
20.670
35.659
14.632
1.00
18.39

850
O
LYS
A
310
20.956
36.276
13.605
1.00
19.24

851
N
TYR
A
311
21.478
34.751
15.174
1.00
16.44

852
CA
TYR
A
311
22.788
34.459
14.601
1.00
19.84

853
CB
TYR
A
311
23.784
34.136
15.719
1.00
23.67

854
CG
TYR
A
311
24.144
35.333
16.568
1.00
27.71

855
CD1
TYR
A
311
24.994
36.325
16.083
1.00
30.38

856
CE1
TYR
A
311
25.315
37.439
16.856
1.00
32.19

857
CD2
TYR
A
311
23.620
35.484
17.850
1.00
30.97

858
CE2
TYR
A
311
23.933
36.595
18.631
1.00
33.09

859
CZ
TYR
A
311
24.782
37.566
18.127
1.00
33.75

860
OH
TYR
A
311
25.107
38.659
18.895
1.00
36.85

861
C
TYR
A
311
22.803
33.336
13.573
1.00
17.92

862
O
TYR
A
311
23.712
33.261
12.743
1.00
20.86

863
N
GLY
A
312
21.799
32.469
13.610
1.00
16.75

864
CA
GLY
A
312
21.784
31.364
12.669
1.00
15.82

865
C
GLY
A
312
20.979
31.509
11.390
1.00
16.03

866
O
GLY
A
312
21.278
30.834
10.403
1.00
16.07

867
N
VAL
A
313
19.971
32.377
11.372
1.00
15.36

868
CA
VAL
A
313
19.154
32.494
10.170
1.00
16.30

869
CB
VAL
A
313
17.975
33.506
10.353
1.00
17.29

870
CG1
VAL
A
313
18.485
34.904
10.609
1.00
16.70

871
CG2
VAL
A
313
17.093
33.486
9.124
1.00
23.41

872
C
VAL
A
313
19.901
32.811
8.878
1.00
14.96

873
O
VAL
A
313
19.631
32.198
7.846
1.00
12.97

874
N
TYR
A
314
20.852
33.738
8.902
1.00
13.63

875
CA
TYR
A
314
21.539
34.047
7.654
1.00
14.50

876
CB
TYR
A
314
22.206
35.429
7.729
1.00
15.24

877
CG
TYR
A
314
21.201
36.518
7.423
1.00
15.95

878
CD1
TYR
A
314
20.785
36.754
6.115
1.00
16.47

879
CE1
TYR
A
314
19.764
37.664
5.838
1.00
17.10

880
CD2
TYR
A
314
20.578
37.230
8.452
1.00
15.91

881
CE2
TYR
A
314
19.563
38.137
8.190
1.00
15.61

882
CZ
TYR
A
314
19.156
38.349
6.883
1.00
16.58

883
OH
TYR
A
314
18.128
39.229
6.619
1.00
17.94

884
C
TYR
A
314
22.514
32.968
7.212
1.00
14.15

885
O
TYR
A
314
22.786
32.827
6.017
1.00
14.15

886
N
GLU
A
315
23.041
32.198
8.159
1.00
12.79

887
CA
GLU
A
315
23.939
31.113
7.776
1.00
13.63

888
CB
GLU
A
315
24.581
30.471
9.012
1.00
15.05

889
CG
GLU
A
315
25.608
31.379
9.701
1.00
15.42

890
CD
GLU
A
315
26.281
30.734
10.900
1.00
16.70

891
OE1
GLU
A
315
26.093
29.520
11.125
1.00
17.95

892
OE2
GLU
A
315
27.008
31.446
11.617
1.00
16.57

893
C
GLU
A
315
23.055
30.102
7.034
1.00
14.04

894
O
GLU
A
315
23.449
29.549
6.007
1.00
12.76

895
N
ALA
A
316
21.842
29.895
7.545
1.00
13.17

896
CA
ALA
A
316
20.906
28.953
6.930
1.00
13.03

897
CB
ALA
A
316
19.701
28.721
7.846
1.00
13.75

898
C
ALA
A
316
20.435
29.488
5.589
1.00
13.24

899
O
ALA
A
316
20.327
28.748
4.612
1.00
12.79

900
N
ILE
A
317
20.146
30.784
5.544
1.00
12.44

901
CA
ILE
A
317
19.693
31.399
4.306
1.00
11.19

902
CB
ILE
A
317
19.360
32.896
4.534
1.00
10.99

903
CG2
ILE
A
317
19.215
33.639
3.193
1.00
11.43

904
CG1
ILE
A
317
18.053
32.999
5.325
1.00
12.81

905
CD1
ILE
A
317
17.711
34.415
5.775
1.00
13.13

906
C
ILE
A
317
20.720
31.242
3.184
1.00
12.02

907
O
ILE
A
317
20.377
30.815
2.082
1.00
12.18

908
N
PHE
A
318
21.980
31.566
3.450
1.00
13.30

909
CA
PHE
A
318
22.982
31.429
2.393
1.00
13.60

910
CB
PHE
A
318
24.275
32.137
2.797
1.00
14.04

911
CG
PHE
A
318
24.095
33.610
3.056
1.00
13.96

912
CD1
PHE
A
318
23.204
34.355
2.287
1.00
16.84

913
CD2
PHE
A
318
24.815
34.252
4.056
1.00
15.29

914
CE1
PHE
A
318
23.030
35.722
2.509
1.00
17.71

915
CE2
PHE
A
318
24.649
35.616
4.285
1.00
18.04

916
CZ
PHE
A
318
23.750
36.350
3.506
1.00
15.92

917
C
PHE
A
318
23.233
29.959
2.024
1.00
13.74

918
O
PHE
A
318
23.540
29.647
0.875
1.00
13.80

919
N
ALA
A
319
23.103
29.054
2.989
1.00
13.03

920
CA
ALA
A
319
23.275
27.631
2.698
1.00
12.43

921
CB
ALA
A
319
23.257
26.807
4.001
1.00
11.53

922
C
ALA
A
319
22.127
27.186
1.781
1.00
13.70

923
O
ALA
A
319
22.340
26.474
0.792
1.00
13.68

924
N
MET
A
320
20.906
27.612
2.102
1.00
12.83

925
CA
MET
A
320
19.754
27.229
1.291
1.00
11.87

926
CB
MET
A
320
18.446
27.436
2.071
1.00
14.42

927
CG
MET
A
320
18.375
26.587
3.347
1.00
16.28

928
SD
MET
A
320
16.760
26.610
4.149
1.00
18.54

929
CE
MET
A
320
16.612
28.349
4.548
1.00
20.41

930
C
MET
A
320
19.690
27.941
−0.060
1.00
13.87

931
O
MET
A
320
19.023
27.464
−0.976
1.00
12.13

932
N
LEU
A
321
20.376
29.077
−0.197
1.00
13.97

933
CA
LEU
A
321
20.371
29.775
−1.485
1.00
15.41

934
CB
LEU
A
321
21.223
31.051
−1.424
1.00
15.37

935
CG
LEU
A
321
20.547
32.292
−0.829
1.00
18.20

936
CD1
LEU
A
321
21.490
33.490
−0.942
1.00
19.32

937
CD2
LEU
A
321
19.231
32.569
−1.561
1.00
18.93

938
C
LEU
A
321
20.935
28.854
−2.560
1.00
13.60

939
O
LEU
A
321
20.499
28.874
−3.712
1.00
15.79

940
N
SER
A
322
21.919
28.052
−2.168
1.00
12.99

941
CA
SER
A
322
22.575
27.121
−3.072
1.00
14.61

942
CB
SER
A
322
23.541
26.240
−2.276
1.00
14.55

943
OG
SER
A
322
24.372
27.042
−1.457
1.00
15.05

944
C
SER
A
322
21.552
26.244
−3.797
1.00
15.16

945
O
SER
A
322
21.734
25.892
−4.963
1.00
16.58

946
N
SER
A
323
20.476
25.899
−3.099
1.00
14.05

947
CA
SER
A
323
19.439
25.051
−3.675
1.00
14.37

948
CB
SER
A
323
18.390
24.708
−2.615
1.00
16.17

949
OG
SER
A
323
18.989
24.036
−1.524
1.00
14.97

950
C
SER
A
323
18.741
25.667
−4.883
1.00
15.39

951
O
SER
A
323
18.260
24.947
−5.759
1.00
15.48

952
N
VAL
A
324
18.672
26.995
−4.927
1.00
16.08

953
CA
VAL
A
324
17.999
27.667
−6.029
1.00
16.93

954
CB
VAL
A
324
16.974
28.713
−5.516
1.00
18.06

955
CG1
VAL
A
324
15.878
28.020
−4.716
1.00
20.27

956
CG2
VAL
A
324
17.674
29.766
−4.667
1.00
19.05

957
C
VAL
A
324
18.967
28.358
−6.973
1.00
16.26

958
O
VAL
A
324
18.551
29.150
−7.816
1.00
17.98

959
N
MET
A
325
20.251
28.034
−6.853
1.00
16.16

960
CA
MET
A
325
21.276
28.648
−7.700
1.00
17.20

961
CB
MET
A
325
22.355
29.329
−6.846
1.00
16.55

962
CG
MET
A
325
21.941
30.527
−6.005
1.00
16.51

963
SD
MET
A
325
23.361
31.079
−4.984
1.00
17.83

964
CE
MET
A
325
22.982
32.821
−4.800
1.00
19.15

965
C
MET
A
325
22.021
27.664
−8.596
1.00
19.13

966
O
MET
A
325
22.098
26.470
−8.308
1.00
20.24

967
N
ASN
A
326
22.557
28.188
−9.694
1.00
19.31

968
CA
ASN
A
326
23.425
27.418
−10.572
1.00
20.10

969
CB
ASN
A
326
22.716
26.858
−11.821
1.00
21.23

970
CG
ASN
A
326
22.149
27.919
−12.730
1.00
20.10

971
OD1
ASN
A
326
22.672
29.028
−12.837
1.00
21.27

972
ND2
ASN
A
326
21.076
27.559
−13.434
1.00
23.09

973
C
ASN
A
326
24.498
28.453
−10.909
1.00
21.45

974
O
ASN
A
326
24.426
29.580
−10.423
1.00
19.65

975
N
LYS
A
327
25.488
28.098
−11.717
1.00
21.83

976
CA
LYS
A
327
26.560
29.043
−12.011
1.00
23.64

977
CB
LYS
A
327
27.655
28.364
−12.841
1.00
26.31

978
CG
LYS
A
327
27.285
28.119
−14.297
1.00
30.33

979
CD
LYS
A
327
28.506
27.647
−15.083
1.00
34.09

980
CE
LYS
A
327
28.258
27.640
−16.589
1.00
36.35

981
NZ
LYS
A
327
27.208
26.665
−16.992
1.00
39.18

982
C
LYS
A
327
26.158
30.342
−12.704
1.00
22.90

983
O
LYS
A
327
26.924
31.308
−12.685
1.00
22.33

984
N
ASP
A
328
24.965
30.387
−13.290
1.00
21.50

985
CA
ASP
A
328
24.544
31.582
−14.020
1.00
21.46

986
CB
ASP
A
328
24.110
31.185
−15.433
1.00
22.79

987
CG
ASP
A
328
25.228
30.535
−16.219
1.00
24.81

988
OD1
ASP
A
328
26.327
31.124
−16.295
1.00
28.16

989
OD2
ASP
A
328
25.010
29.440
−16.760
1.00
26.38

990
C
ASP
A
328
23.462
32.463
−13.404
1.00
19.81

991
O
ASP
A
328
23.123
33.505
−13.967
1.00
18.99

992
N
GLY
A
329
22.915
32.061
−12.263
1.00
18.40

993
CA
GLY
A
329
21.879
32.872
−11.648
1.00
17.35

994
C
GLY
A
329
21.093
32.134
−10.584
1.00
16.28

995
O
GLY
A
329
21.466
31.030
−10.186
1.00
15.47

996
N
MET
A
330
20.002
32.739
−10.120
1.00
17.05

997
CA
MET
A
330
19.183
32.109
−9.089
1.00
17.55

998
CB
MET
A
330
19.563
32.642
−7.701
1.00
19.90

999
CG
MET
A
330
19.221
34.098
−7.438
1.00
22.04

1000
SD
MET
A
330
19.415
34.525
−5.667
1.00
24.36

1001
CE
MET
A
330
17.856
34.142
−5.014
1.00
23.38

1002
C
MET
A
330
17.689
32.295
−9.308
1.00
17.11

1003
O
MET
A
330
17.249
33.259
−9.930
1.00
17.45

1004
N
LEU
A
331
16.908
31.350
−8.799
1.00
16.64

1005
CA
LEU
A
331
15.460
31.411
−8.912
1.00
16.30

1006
CB
LEU
A
331
14.843
30.051
−8.595
1.00
17.42

1007
CG
LEU
A
331
15.026
28.943
−9.620
1.00
19.04

1008
CD1
LEU
A
331
14.408
27.650
−9.079
1.00
18.84

1009
CD2
LEU
A
331
14.363
29.359
−10.925
1.00
17.82

1010
C
LEU
A
331
14.930
32.414
−7.903
1.00
16.49

1011
O
LEU
A
331
15.415
32.465
−6.774
1.00
17.61

1012
N
VAL
A
332
13.932
33.194
−8.305
1.00
14.86

1013
CA
VAL
A
332
13.331
34.173
−7.409
1.00
15.11

1014
CB
VAL
A
332
13.880
35.603
−7.664
1.00
14.89

1015
CG1
VAL
A
332
15.406
35.600
−7.537
1.00
17.85

1016
CG2
VAL
A
332
13.453
36.099
−9.040
1.00
16.47

1017
C
VAL
A
332
11.821
34.193
−7.589
1.00
14.36

1018
O
VAL
A
332
11.283
33.559
−8.501
1.00
15.87

1019
N
ALA
A
333
11.148
34.928
−6.713
1.00
13.97

1020
CA
ALA
A
333
9.698
35.071
−6.757
1.00
14.91

1021
CB
ALA
A
333
9.294
35.898
−7.977
1.00
15.58

1022
C
ALA
A
333
8.978
33.724
−6.768
1.00
14.63

1023
O
ALA
A
333
8.168
33.441
−7.660
1.00
14.60

1024
N
TYR
A
334
9.285
32.899
−5.772
1.00
14.26

1025
CA
TYR
A
334
8.660
31.589
−5.630
1.00
15.27

1026
CB
TYR
A
334
7.195
31.781
−5.230
1.00
15.76

1027
CG
TYR
A
334
7.086
32.362
−3.840
1.00
18.04

1028
CD1
TYR
A
334
7.025
31.532
−2.722
1.00
19.51

1029
CE1
TYR
A
334
7.073
32.055
−1.432
1.00
20.29

1030
CD2
TYR
A
334
7.182
33.737
−3.634
1.00
19.02

1031
CE2
TYR
A
334
7.237
34.272
−2.348
1.00
20.93

1032
CZ
TYR
A
334
7.186
33.427
−1.253
1.00
20.76

1033
OH
TYR
A
334
7.284
33.950
0.019
1.00
21.61

1034
C
TYR
A
334
8.797
30.715
−6.871
1.00
14.54

1035
O
TYR
A
334
7.854
30.038
−7.290
1.00
15.22

1036
N
GLY
A
335
9.996
30.744
−7.441
1.00
15.09

1037
CA
GLY
A
335
10.306
29.944
−8.612
1.00
16.73

1038
C
GLY
A
335
9.795
30.441
−9.946
1.00
18.37

1039
O
GLY
A
335
9.965
29.761
−10.958
1.00
18.69

1040
N
ASN
A
336
9.188
31.623
−9.972
1.00
18.57

1041
CA
ASN
A
336
8.654
32.133
−11.227
1.00
18.81

1042
CB
ASN
A
336
7.322
32.835
−10.988
1.00
21.87

1043
CG
ASN
A
336
6.149
31.866
−10.981
1.00
24.72

1044
OD1
ASN
A
336
5.003
32.275
−10.900
1.00
32.52

1045
ND2
ASN
A
336
6.437
30.579
−11.071
1.00
29.15

1046
C
ASN
A
336
9.595
33.053
−11.993
1.00
18.54

1047
O
ASN
A
336
9.277
33.492
−13.096
1.00
16.73

1048
N
GLY
A
337
10.749
33.335
−11.406
1.00
16.20

1049
CA
GLY
A
337
11.717
34.187
−12.066
1.00
16.52

1050
C
GLY
A
337
13.114
33.638
−11.886
1.00
16.47

1051
O
GLY
A
337
13.347
32.809
−11.008
1.00
15.40

1052
N
PHE
A
338
14.041
34.090
−12.728
1.00
15.82

1053
CA
PHE
A
338
15.436
33.672
−12.654
1.00
15.40

1054
CB
PHE
A
338
15.722
32.543
−13.651
1.00
16.65

1055
CG
PHE
A
338
17.156
32.066
−13.641
1.00
20.70

1056
CD1
PHE
A
338
18.113
32.664
−14.464
1.00
19.82

1057
CD2
PHE
A
338
17.548
31.021
−12.808
1.00
19.54

1058
CE1
PHE
A
338
19.433
32.225
−14.460
1.00
22.34

1059
CE2
PHE
A
338
18.873
30.570
−12.794
1.00
22.09

1060
CZ
PHE
A
338
19.816
31.174
−13.624
1.00
22.09

1061
C
PHE
A
338
16.265
34.904
−12.994
1.00
16.41

1062
O
PHE
A
338
16.212
35.411
−14.117
1.00
15.80

1063
N
ILE
A
339
17.014
35.397
−12.015
1.00
14.27

1064
CA
ILE
A
339
17.828
36.581
−12.229
1.00
15.49

1065
CB
ILE
A
339
17.689
37.550
−11.028
1.00
15.76

1066
CG2
ILE
A
339
18.192
36.892
−9.760
1.00
17.30

1067
CG1
ILE
A
339
18.434
38.853
−11.311
1.00
15.24

1068
CD1
ILE
A
339
17.955
39.999
−10.429
1.00
16.30

1069
C
ILE
A
339
19.274
36.151
−12.453
1.00
16.57

1070
O
ILE
A
339
19.835
35.379
−11.676
1.00
16.99

1071
N
THR
A
340
19.884
36.644
−13.526
1.00
15.69

1072
CA
THR
A
340
21.251
36.232
−13.835
1.00
17.54

1073
CB
THR
A
340
21.625
36.501
−15.321
1.00
18.08

1074
OG1
THR
A
340
21.680
37.913
−15.563
1.00
18.08

1075
CG2
THR
A
340
20.611
35.876
−16.239
1.00
19.40

1076
C
THR
A
340
22.337
36.840
−12.973
1.00
17.79

1077
O
THR
A
340
22.272
38.001
−12.551
1.00
17.03

1078
N
ARG
A
341
23.347
36.019
−12.729
1.00
18.29

1079
CA
ARG
A
341
24.503
36.395
−11.944
1.00
20.41

1080
CB
ARG
A
341
25.470
35.216
−11.910
1.00
20.86

1081
CG
ARG
A
341
26.710
35.443
−11.093
1.00
23.49

1082
CD
ARG
A
341
27.502
34.152
−11.003
1.00
22.29

1083
NE
ARG
A
341
28.625
34.282
−10.089
1.00
25.39

1084
CZ
ARG
A
341
29.432
33.283
−9.755
1.00
25.74

1085
NH1
ARG
A
341
29.239
32.074
−10.264
1.00
25.82

1086
NH2
ARG
A
341
30.427
33.495
−8.908
1.00
25.63

1087
C
ARG
A
341
25.175
37.606
−12.587
1.00
20.85

1088
O
ARG
A
341
25.630
38.515
−11.900
1.00
20.39

1089
N
GLU
A
342
25.225
37.615
−13.915
1.00
21.71

1090
CA
GLU
A
342
25.858
38.717
−14.633
1.00
23.42

1091
CB
GLU
A
342
26.044
38.343
−16.104
1.00
26.93

1092
CG
GLU
A
342
27.151
37.324
−16.330
1.00
31.26

1093
CD
GLU
A
342
28.501
37.816
−15.832
1.00
33.51

1094
OE1
GLU
A
342
28.961
38.882
−16.294
1.00
36.23

1095
OE2
GLU
A
342
29.105
37.140
−14.977
1.00
36.72

1096
C
GLU
A
342
25.101
40.037
−14.510
1.00
21.78

1097
O
GLU
A
342
25.715
41.103
−14.425
1.00
23.51

1098
N
PUB
A
343
23.774
39.974
−14.496
1.00
20.79

1099
CA
PUB
A
343
22.982
41.188
−14.358
1.00
20.13

1100
CB
PHE
A
343
21.491
40.880
−14.534
1.00
21.21

1101
CG
PHE
A
343
20.598
42.065
−14.304
1.00
22.31

1102
CD1
PHE
A
343
20.800
43.255
−15.003
1.00
22.58

1103
CD2
PHE
A
343
19.556
41.998
−13.385
1.00
22.12

1104
CE1
PUB
A
343
19.978
44.356
−14.784
1.00
22.50

1105
CE2
PHE
A
343
18.729
43.095
−13.159
1.00
21.07

1106
CZ
PUB
A
343
18.940
44.277
−13.861
1.00
23.38

1107
C
PHE
A
343
23.237
41.787
−12.973
1.00
20.06

1108
O
PHE
A
343
23.389
42.998
−12.821
1.00
18.10

1109
N
LEU
A
344
23.291
40.929
−11.959
1.00
19.09

1110
CA
LEU
A
344
23.535
41.390
−10.599
1.00
19.98

1111
CB
LEU
A
344
23.434
40.211
−9.629
1.00
18.81

1112
CG
LEU
A
344
22.003
39.699
−9.449
1.00
17.36

1113
CD1
LEU
A
344
22.030
38.298
−8.865
1.00
17.66

1114
CD2
LEU
A
344
21.222
40.668
−8.541
1.00
18.64

1115
C
LEU
A
344
24.891
42.082
−10.451
1.00
20.25

1116
O
LEU
A
344
25.000
43.113
−9.785
1.00
20.17

1117
N
LYS
A
345
25.926
41.532
−11.077
1.00
22.58

1118
CA
LYS
A
345
27.243
42.149
−10.976
1.00
25.12

1119
CB
LYS
A
345
28.329
41.149
−11.388
1.00
28.30

1120
CG
LYS
A
345
28.086
40.453
−12.709
1.00
31.49

1121
CD
LYS
A
345
28.931
39.185
−12.824
1.00
34.20

1122
CE
LYS
A
345
30.418
39.474
−12.663
1.00
32.93

1123
NZ
LYS
A
345
31.242
38.267
−12.935
1.00
33.54

1124
C
LYS
A
345
27.349
43.442
−11.787
1.00
26.38

1125
O
LYS
A
345
28.246
44.259
−11.551
1.00
28.05

1126
N
SER
A
346
26.411
43.644
−12.713
1.00
25.99

1127
CA
SER
A
346
26.397
44.840
−13.557
1.00
25.78

1128
CB
SER
A
346
25.596
44.590
−14.834
1.00
27.38

1129
OG
SER
A
346
24.206
44.742
−14.590
1.00
27.61

1130
C
SER
A
346
25.782
46.028
−12.832
1.00
25.54

1131
O
SER
A
346
25.870
47.169
−13.298
1.00
24.80

1132
N
LEU
A
347
25.151
45.762
−11.694
1.00
21.74

1133
CA
LEU
A
347
24.529
46.826
−10.925
1.00
21.47

1134
CB
LEU
A
347
23.686
46.242
−9.790
1.00
20.68

1135
CG
LEU
A
347
22.544
45.312
−10.207
1.00
17.94

1136
CD1
LEU
A
347
21.932
44.695
−8.952
1.00
17.43

1137
CD2
LEU
A
347
21.497
46.094
−10.998
1.00
18.91

1138
C
LEU
A
347
25.585
47.751
−10.341
1.00
22.34

1139
O
LEU
A
347
26.773
47.431
−10.306
1.00
21.32

1140
N
ARG
A
348
25.133
48.904
−9.878
1.00
23.03

1141
CA
ARG
A
348
26.007
49.899
−9.279
1.00
24.90

1142
CB
ARG
A
348
25.247
51.233
−9.226
1.00
26.16

1143
CG
ARG
A
348
25.445
52.062
−7.977
1.00
28.63

1144
CD
ARG
A
348
24.782
53.424
−8.123
1.00
27.93

1145
NE
ARG
A
348
23.514
53.557
−7.407
1.00
25.84

1146
CZ
ARG
A
348
23.385
53.485
−6.086
1.00
25.53

1147
NH1
ARG
A
348
24.446
53.264
−5.318
1.00
26.92

1148
NH2
ARG
A
348
22.201
53.676
−5.526
1.00
26.63

1149
C
ARG
A
348
26.431
49.457
−7.877
1.00
23.21

1150
O
ARG
A
348
25.666
48.796
−7.177
1.00
22.61

1151
N
LYS
A
349
27.654
49.799
−7.472
1.00
23.12

1152
CA
LYS
A
349
28.104
49.457
−6.126
1.00
22.49

1153
CB
LYS
A
349
29.575
49.848
−5.910
1.00
23.58

1154
CG
LYS
A
349
30.585
49.055
−6.738
1.00
22.91

1155
CD
LYS
A
349
32.017
49.580
−6.540
1.00
25.76

1156
CE
LYS
A
349
32.665
49.069
−5.261
1.00
26.68

1157
NZ
LYS
A
349
33.144
47.662
−5.407
1.00
28.29

1158
C
LYS
A
349
27.218
50.268
−5.188
1.00
22.76

1159
O
LYS
A
349
26.765
51.361
−5.545
1.00
24.51

1160
N
PRO
A
350
26.975
49.767
−3.970
1.00
21.69

1161
CD
PRO
A
350
26.248
50.523
−2.935
1.00
23.55

1162
CA
PRO
A
350
27.476
48.506
−3.421
1.00
21.20

1163
CB
PRO
A
350
27.573
48.818
−1.943
1.00
23.13

1164
CG
PRO
A
350
26.312
49.586
−1.724
1.00
22.88

1165
C
PRO
A
350
26.544
47.322
−3.685
1.00
20.65

1166
O
PRO
A
350
26.815
46.197
−3.256
1.00
20.59

1167
N
PHE
A
351
25.447
47.576
−4.387
1.00
19.16

1168
CA
PHE
A
351
24.475
46.525
−4.666
1.00
18.85

1169
CB
PHE
A
351
23.252
47.140
−5.349
1.00
20.28

1170
CG
PHE
A
351
22.539
48.141
−4.487
1.00
19.94

1171
CD1
PHE
A
351
21.737
47.720
−3.427
1.00
18.19

1172
CD2
PHE
A
351
22.720
49.507
−4.690
1.00
18.89

1173
CE1
PHE
A
351
21.125
48.645
−2.576
1.00
19.37

1174
CE2
PHE
A
351
22.115
50.436
−3.848
1.00
19.54

1175
CZ
PHE
A
351
21.316
50.005
−2.786
1.00
19.87

1176
C
PHE
A
351
25.040
45.361
−5.469
1.00
19.99

1177
O
PHE
A
351
24.620
44.213
−5.289
1.00
19.11

1178
N
CYS
A
352
26.011
45.642
−6.334
1.00
17.57

1179
CA
CYS
A
352
26.622
44.589
−7.138
1.00
18.30

1180
CB
CYS
A
352
27.358
45.197
−8.335
1.00
18.99

1181
SG
CYS
A
352
28.659
46.372
−7.868
1.00
20.67

1182
C
CYS
A
352
27.599
43.760
−6.307
1.00
18.14

1183
O
CYS
A
352
28.107
42.743
−6.772
1.00
17.82

1184
N
ASP
A
353
27.843
44.184
−5.069
1.00
18.21

1185
CA
ASP
A
353
28.781
43.477
−4.206
1.00
18.60

1186
CB
ASP
A
353
29.640
44.484
−3.439
1.00
20.06

1187
CG
ASP
A
353
30.432
45.395
−4.364
1.00
20.29

1188
OD1
ASP
A
353
31.032
44.880
−5.319
1.00
21.00

1189
OD2
ASP
A
353
30.457
46.621
−4.137
1.00
22.31

1190
C
ASP
A
353
28.109
42.533
−3.223
1.00
19.14

1191
O
ASP
A
353
28.771
41.917
−2.386
1.00
20.18

1192
N
ILE
A
354
26.794
42.410
−3.340
1.00
17.15

1193
CA
ILE
A
354
26.023
41.562
−2.445
1.00
18.64

1194
CB
ILE
A
354
24.539
42.001
−2.422
1.00
19.28

1195
CG2
ILE
A
354
23.727
41.075
−1.521
1.00
17.16

1196
CG1
ILE
A
354
24.431
43.451
−1.940
1.00
19.43

1197
CD1
ILE
A
354
23.014
43.997
−1.956
1.00
19.79

1198
C
ILE
A
354
26.042
40.074
−2.778
1.00
18.41

1199
O
ILE
A
354
26.427
39.245
−1.951
1.00
17.58

1200
N
MET
A
355
25.630
39.743
−3.996
1.00
20.04

1201
CA
MET
A
355
25.507
38.349
−4.406
1.00
18.56

1202
CB
MET
A
355
24.429
38.241
−5.490
1.00
19.49

1203
CG
MET
A
355
23.033
38.634
−5.014
1.00
20.24

1204
SD
MET
A
355
22.487
37.687
−3.565
1.00
20.20

1205
CB
MET
A
355
22.589
36.017
−4.219
1.00
16.96

1206
C
MET
A
355
26.702
37.497
−4.821
1.00
18.99

1207
O
MET
A
355
26.655
36.283
−4.637
1.00
17.53

1208
N
GLU
A
356
27.764
38.084
−5.373
1.00
19.55

1209
CA
GLU
A
356
28.904
37.265
−5.800
1.00
19.92

1210
CB
GLU
A
356
30.072
38.135
−6.292
1.00
21.97

1211
CG
GLU
A
356
30.017
38.502
−7.762
1.00
26.26

1212
CD
GLU
A
356
29.835
37.292
−8.663
1.00
27.30

1213
OE1
GLU
A
356
28.697
37.049
−9.107
1.00
26.68

1214
OE2
GLU
A
356
30.826
36.575
−8.920
1.00
29.91

1215
C
GLU
A
356
29.432
36.288
−4.752
1.00
18.52

1216
O
GLU
A
356
29.624
35.112
−5.046
1.00
18.23

1217
N
PRO
A
357
29.686
36.758
−3.522
1.00
18.98

1218
CD
PRO
A
357
29.538
38.130
−3.001
1.00
20.10

1219
CA
PRO
A
357
30.195
35.863
−2.477
1.00
19.09

1220
CB
PRO
A
357
30.290
36.777
−1.259
1.00
20.02

1221
CG
PRO
A
357
30.525
38.137
−1.869
1.00
20.53

1222
C
PRO
A
357
29.273
34.664
−2.217
1.00
17.84

1223
O
PRO
A
357
29.730
33.572
−1.869
1.00
15.96

1224
N
LYS
A
358
27.973
34.883
−2.379
1.00
17.85

1225
CA
LYS
A
358
26.984
33.832
−2.161
1.00
16.69

1226
CB
LYS
A
358
25.594
34.448
−1.963
1.00
17.55

1227
CG
LYS
A
358
25.399
35.180
−0.625
1.00
16.13

1228
CD
LYS
A
358
26.255
36.439
−0.520
1.00
18.57

1229
CE
LYS
A
358
25.812
37.337
0.632
1.00
16.06

1230
NZ
LYS
A
358
26.664
38.570
0.749
1.00
15.29

1231
C
LYS
A
358
26.961
32.848
−3.327
1.00
17.68

1232
O
LYS
A
358
26.787
31.638
−3.132
1.00
17.04

1233
N
PHE
A
359
27.122
33.359
−4.544
1.00
17.39

1234
CA
PHE
A
359
27.153
32.478
−5.709
1.00
16.62

1235
CB
PHE
A
359
27.167
33.290
−7.012
1.00
16.38

1236
CG
PHE
A
359
25.795
33.651
−7.523
1.00
18.08

1237
GD1
PHE
A
359
24.944
32.671
−8.037
1.00
17.39

1238
CD2
PHE
A
359
25.355
34.970
−7.497
1.00
16.89

1239
CE1
PHE
A
359
23.679
33.004
−8.514
1.00
17.41

1240
CE2
PHE
A
359
24.093
35.313
−7.970
1.00
16.42

1241
CZ
PHE
A
359
23.253
34.327
−8.481
1.00
16.76

1242
C
PHE
A
359
28.421
31.633
−5.598
1.00
16.15

1243
O
PHE
A
359
28.400
30.424
−5.851
1.00
16.24

1244
N
ASP
A
360
29.526
32.263
−5.201
1.00
18.27

1245
CA
ASP
A
360
30.777
31.519
−5.050
1.00
18.69

1246
CB
ASP
A
360
31.948
32.453
−4.710
1.00
20.51

1247
CG
ASP
A
360
32.445
33.229
−5.922
1.00
22.65

1248
OD1
ASP
A
360
32.334
32.705
−7.048
1.00
23.09

1249
OD2
ASP
A
360
32.958
34.354
−5.752
1.00
27.87

1250
C
ASP
A
360
30.637
30.432
−3.988
1.00
18.16

1251
O
ASP
A
360
31.115
29.311
−4.177
1.00
17.43

1252
N
PHE
A
361
29.975
30.745
−2.876
1.00
16.51

1253
CA
PHE
A
361
29.793
29.736
−1.838
1.00
17.11

1254
OB
PHE
A
361
29.160
30.326
−0.574
1.00
17.43

1255
CG
PHE
A
361
28.769
29.280
0.441
1.00
16.12

1256
CD1
PHE
A
361
27.557
28.600
0.328
1.00
15.11

1257
CD2
PHE
A
361
29.642
28.927
1.469
1.00
16.71

1258
CE1
PHE
A
361
27.219
27.580
1.223
1.00
14.11

1259
CE2
PHE
A
361
29.314
27.909
2.367
1.00
15.23

1260
CZ
PHE
A
361
28.101
27.235
2.242
1.00
11.27

1261
C
PHE
A
361
28.905
28.605
−2.347
1.00
16.98

1262
O
PHE
A
361
29.211
27.431
−2.147
1.00
16.87

1263
N
ALA
A
362
27.803
28.971
−2.994
1.00
16.32

1264
CA
ALA
A
362
26.851
27.993
−3.517
1.00
19.25

1265
CB
ALA
A
362
25.659
28.714
−4.145
1.00
17.22

1266
C
ALA
A
362
27.460
27.021
−4.528
1.00
19.60

1267
O
ALA
A
362
27.080
25.850
−4.579
1.00
20.69

1268
N
MET
A
363
28.396
27.502
−5.337
1.00
19.90

1269
CA
MET
A
363
29.021
26.649
−6.343
1.00
23.22

1270
CB
MET
A
363
29.940
27.473
−7.244
1.00
25.16

1271
CG
MET
A
363
29.601
27.362
−8.717
1.00
31.86

1272
SD
MET
A
363
27.851
27.659
−9.059
1.00
35.24

1273
CE
MET
A
363
27.233
25.996
−9.144
1.00
37.40

1274
C
MET
A
363
29.808
25.533
−5.672
1.00
22.48

1275
O
MET
A
363
29.718
24.373
−6.069
1.00
22.07

1276
N
LYS
A
364
30.576
25.884
−4.647
1.00
21.68

1277
CA
LYS
A
364
31.349
24.884
−3.932
1.00
22.55

1278
CB
LYS
A
364
32.446
25.564
−3.104
1.00
24.59

1279
CG
LYS
A
364
33.595
26.061
−3.982
1.00
28.52

1280
CD
LYS
A
364
34.721
26.718
−3.203
1.00
31.12

1281
CE
LYS
A
364
34.316
28.080
−2.674
1.00
33.08

1282
NZ
LYS
A
364
35.512
28.842
−2.220
1.00
34.91

1283
C
LYS
A
364
30.438
24.022
−3.056
1.00
22.72

1284
O
LYS
A
364
30.699
22.834
−2.861
1.00
22.63

1285
N
PHE
A
365
29.358
24.610
−2.547
1.00
21.24

1286
CA
PHE
A
365
28.429
23.855
−1.705
1.00
20.87

1287
CB
PHE
A
365
27.423
24.794
−1.027
1.00
19.09

1288
CG
PHE
A
365
26.652
24.151
0.098
1.00
19.22

1289
CD1
PHE
A
365
27.263
23.902
1.322
1.00
19.37

1290
CD2
PHE
A
365
25.311
23.807
−0.063
1.00
19.20

1291
CE1
PHE
A
365
26.547
23.321
2.376
1.00
18.07

1292
CE2
PHE
A
365
24.585
23.227
0.978
1.00
18.27

1293
CZ
PHE
A
365
25.204
22.984
2.202
1.00
18.45

1294
C
PHE
A
365
27.667
22.819
−2.532
1.00
20.34

1295
O
PHE
A
365
27.492
21.672
−2.106
1.00
19.46

1296
N
ASN
A
366
27.212
23.232
−3.712
1.00
20.08

1297
CA
ASN
A
366
26.463
22.354
−4.606
1.00
21.22

1298
CB
ASN
A
366
25.910
23.158
−5.789
1.00
21.85

1299
CG
ASN
A
366
24.619
23.893
−5.448
1.00
22.68

1300
OD1
ASN
A
366
24.237
24.853
−6.124
1.00
22.40

1301
ND2
ASN
A
366
23.935
23.434
−4.406
1.00
20.32

1302
C
ASN
A
366
27.324
21.202
−5.120
1.00
21.97

1303
O
ASN
A
366
26.806
20.147
−5.495
1.00
22.05

1304
N
ALA
A
367
28.636
21.409
−5.132
1.00
20.80

1305
CA
ALA
A
367
29.564
20.381
−5.587
1.00
22.52

1306
CB
ALA
A
367
30.977
20.942
−5.660
1.00
22.39

1307
C
ALA
A
367
29.519
19.188
−4.638
1.00
23.80

1308
O
ALA
A
367
30.003
18.102
−4.969
1.00
24.70

1309
N
LEU
A
368
28.942
19.395
−3.455
1.00
22.37

1310
CA
LEU
A
368
28.820
18.328
−2.466
1.00
23.08

1311
CB
LEU
A
368
28.576
18.913
−1.070
1.00
23.25

1312
CG
LEU
A
368
29.713
19.763
−0.491
1.00
23.11

1313
CD1
LEU
A
368
29.369
20.196
0.932
1.00
22.57

1314
CD2
LEU
A
368
31.002
18.960
−0.492
1.00
24.48

1315
C
LEU
A
368
27.681
17.382
−2.834
1.00
22.79

1316
O
LEU
A
368
27.542
16.306
−2.250
1.00
22.44

1317
N
GLU
A
369
26.862
17.796
−3.796
1.00
22.82

1318
CA
GLU
A
369
25.744
16.983
−4.260
1.00
24.48

1319
CB
GLU
A
369
26.279
15.731
−4.955
1.00
26.99

1320
CG
GLU
A
369
26.173
15.757
−6.461
1.00
33.00

1321
CD
GLU
A
369
26.960
14.633
−7.104
1.00
35.36

1322
OE1
GLU
A
369
26.965
13.513
−6.547
1.00
37.48

1323
OE2
GLU
A
369
27.568
14.870
−8.166
1.00
36.92

1324
C
GLU
A
369
24.778
16.571
−3.155
1.00
22.38

1325
O
GLU
A
369
24.286
15.445
−3.144
1.00
23.39

1326
N
LEU
A
370
24.507
17.476
−2.221
1.00
21.57

1327
CA
LEU
A
370
23.586
17.168
−1.133
1.00
18.06

1328
CB
LEU
A
370
23.717
18.197
−0.009
1.00
18.81

1329
CG
LEU
A
370
25.064
18.386
0.688
1.00
16.97

1330
CD1
LEU
A
370
24.875
19.342
1.856
1.00
16.61

1331
CD2
LEU
A
370
25.578
17.044
1.194
1.00
18.25

1332
C
LEU
A
370
22.148
17.199
−1.635
1.00
18.75

1333
O
LEU
A
370
21.845
17.849
−2.639
1.00
19.00

1334
N
ASP
A
371
21.272
16.476
−0.947
1.00
19.17

1335
CA
ASP
A
371
19.860
16.477
−1.292
1.00
18.60

1336
CB
ASP
A
371
19.336
15.060
−1.583
1.00
19.63

1337
CG
ASP
A
371
19.486
14.118
−0.411
1.00
21.42

1338
OD1
ASP
A
371
19.258
14.547
0.738
1.00
18.99

1339
OD2
ASP
A
371
19.813
12.934
−0.647
1.00
24.09

1340
C
ASP
A
371
19.152
17.091
−0.090
1.00
18.66

1341
O
ASP
A
371
19.789
17.388
0.919
1.00
19.31

1342
N
ASP
A
372
17.845
17.287
−0.190
1.00
18.35

1343
CA
ASP
A
372
17.098
17.902
0.896
1.00
18.08

1344
CB
ASP
A
372
15.641
18.084
0.477
1.00
20.09

1345
CG
ASP
A
372
15.487
19.092
−0.654
1.00
21.21

1346
OD1
ASP
A
372
15.925
20.253
−0.478
1.00
20.02

1347
OD2
ASP
A
372
14.932
18.728
−1.717
1.00
22.56

1348
C
ASP
A
372
17.189
17.174
2.236
1.00
17.57

1349
O
ASP
A
372
17.165
17.816
3.285
1.00
17.01

1350
N
SER
A
373
17.298
15.848
2.224
1.00
16.66

1351
CA
SER
A
373
17.406
15.132
3.493
1.00
17.74

1352
CB
SER
A
373
17.371
13.602
3.285
1.00
16.26

1353
OG
SER
A
373
18.514
13.111
2.609
1.00
18.96

1354
C
SER
A
373
18.697
15.552
4.201
1.00
17.27

1355
O
SER
A
373
18.723
15.696
5.423
1.00
19.27

1356
N
ASP
A
374
19.763
15.765
3.433
1.00
16.48

1357
CA
ASP
A
374
21.045
16.188
4.007
1.00
15.88

1358
CB
ASP
A
374
22.174
16.142
2.969
1.00
15.19

1359
CG
ASP
A
374
22.316
14.795
2.301
1.00
18.19

1360
OD1
ASP
A
374
22.362
13.768
3.014
1.00
19.73

1361
OD2
ASP
A
374
22.404
14.777
1.053
1.00
17.35

1362
C
ASP
A
374
20.947
17.631
4.494
1.00
15.34

1363
O
ASP
A
374
21.355
17.954
5.608
1.00
13.16

1364
N
ILE
A
375
20.418
18.492
3.629
1.00
14.16

1365
CA
ILE
A
375
20.283
19.912
3.924
1.00
14.77

1366
CB
ILE
A
375
19.667
20.661
2.713
1.00
14.32

1367
CG2
ILE
A
375
19.457
22.126
3.054
1.00
13.42

1368
CG1
ILE
A
375
20.598
20.528
1.506
1.00
12.81

1369
CD1
ILE
A
375
19.942
20.836
0.159
1.00
10.35

1370
C
ILE
A
375
19.456
20.185
5.178
1.00
15.58

1371
O
ILE
A
375
19.812
21.039
5.993
1.00
15.62

1372
N
SER
A
376
18.363
19.449
5.347
1.00
15.94

1373
CA
SER
A
376
17.517
19.656
6.516
1.00
17.39

1374
CR
SER
A
376
16.329
18.691
6.509
1.00
18.46

1375
OG
SER
A
376
16.754
17.354
6.681
1.00
19.88

1376
C
SER
A
376
18.313
19.472
7.799
1.00
16.76

1377
O
SER
A
376
18.141
20.231
8.740
1.00
15.46

1378
N
LEU
A
377
19.179
18.462
7.839
1.00
17.17

1379
CA
LEU
A
377
19.985
18.213
9.036
1.00
18.15

1380
CB
LEU
A
377
20.649
16.825
8.966
1.00
18.31

1381
CG
LEU
A
377
19.691
15.629
8.897
1.00
20.80

1382
CD1
LEU
A
377
20.471
14.320
8.902
1.00
22.15

1383
CD2
LEU
A
377
18.737
15.675
10.085
1.00
22.01

1384
C
LEU
A
377
21.058
19.285
9.203
1.00
17.32

1385
O
LEU
A
377
21.344
19.720
10.317
1.00
17.55

1386
N
PHE
A
378
21.650
19.697
8.085
1.00
15.68

1387
CA
PHE
A
378
22.694
20.723
8.085
1.00
15.42

1388
CB
PHE
A
378
23.185
20.951
6.652
1.00
14.83

1389
CG
PHE
A
378
24.352
21.895
6.547
1.00
17.91

1390
CD1
PHE
A
378
25.627
21.491
6.928
1.00
18.12

1391
CD2
PHE
A
378
24.172
23.191
6.070
1.00
17.17

1392
CE1
PHE
A
378
26.709
22.364
6.835
1.00
19.84

1393
CE2
PHE
A
378
25.248
24.072
5.974
1.00
17.27

1394
CZ
PHE
A
378
26.519
23.657
6.357
1.00
18.98

1395
C
PHE
A
378
22.138
22.032
8.664
1.00
14.65

1396
O
PHE
A
378
22.778
22.688
9.489
1.00
14.80

1397
N
VAL
A
379
20.937
22.403
8.230
1.00
14.52

1398
CA
VAL
A
379
20.305
23.625
8.713
1.00
13.14

1399
CB
VAL
A
379
19.060
23.964
7.861
1.00
14.31

1400
CG1
VAL
A
379
18.258
25.093
8.492
1.00
13.46

1401
CG2
VAL
A
379
19.520
24.388
6.460
1.00
13.68

1402
C
VAL
A
379
19.945
23.536
10.200
1.00
14.97

1403
O
VAL
A
379
20.093
24.511
10.942
1.00
14.16

1404
N
ALA
A
380
19.479
22.372
10.642
1.00
14.60

1405
CA
ALA
A
380
19.139
22.212
12.055
1.00
15.75

1406
CB
ALA
A
380
18.541
20.830
12.313
1.00
14.49

1407
C
ALA
A
380
20.412
22.389
12.875
1.00
17.48

1408
O
ALA
A
380
20.388
22.955
13.967
1.00
18.76

1409
N
ALA
A
381
21.521
21.890
12.337
1.00
17.47

1410
CA
ALA
A
381
22.809
21.989
13.008
1.00
18.52

1411
CB
ALA
A
381
23.843
21.138
12.275
1.00
18.08

1412
C
ALA
A
381
23.295
23.440
13.116
1.00
18.95

1413
O
ALA
A
381
23.826
23.843
14.149
1.00
18.98

1414
N
ILE
A
382
23.120
24.237
12.065
1.00
18.97

1415
CA
ILE
A
382
23.582
25.621
12.157
1.00
19.61

1416
CB
ILE
A
382
23.589
26.346
10.767
1.00
22.32

1417
CG2
ILE
A
382
24.054
25.408
9.685
1.00
22.00

1418
CG1
ILE
A
382
22.217
26.918
10.442
1.00
25.81

1419
CD1
ILE
A
382
21.988
28.285
11.051
1.00
26.92

1420
C
ILE
A
382
22.722
26.408
13.152
1.00
19.24

1421
O
ILE
A
382
23.223
27.278
13.869
1.00
18.21

1422
N
ILE
A
383
21.434
26.086
13.209
1.00
17.90

1423
CA
ILE
A
383
20.518
26.775
14.113
1.00
18.91

1424
CB
ILE
A
383
19.049
26.426
13.786
1.00
20.25

1425
CG2
ILE
A
383
18.122
26.923
14.899
1.00
20.50

1426
CG1
ILE
A
383
18.655
27.055
12.446
1.00
19.74

1427
CD1
ILE
A
383
17.224
26.779
12.032
1.00
20.27

1428
C
ILE
A
383
20.788
26.438
15.578
1.00
19.83

1429
O
ILE
A
383
20.882
27.328
16.426
1.00
18.98

1430
N
CYS
A
384
20.930
25.154
15.876
1.00
21.71

1431
CA
CYS
A
384
21.169
24.735
17.253
1.00
24.63

1432
CB
CYS
A
384
20.583
23.343
17.466
1.00
26.05

1433
SG
CYS
A
384
18.829
23.300
17.088
1.00
27.14

1434
C
CYS
A
384
22.653
24.763
17.576
1.00
25.29

1435
O
CYS
A
384
23.277
23.732
17.827
1.00
26.58

1436
N
CYS
A
385
23.197
25.974
17.564
1.00
27.00

1437
CA
CYS
A
385
24.605
26.233
17.822
1.00
28.30

1438
CB
CYS
A
385
25.104
27.255
16.804
1.00
30.14

1439
SG
CYS
A
385
26.815
27.715
16.976
1.00
32.84

1440
C
CYS
A
385
24.816
26.764
19.243
1.00
27.82

1441
O
CYS
A
385
24.267
27.801
19.615
1.00
27.12

1442
N
GLY
A
386
25.624
26.055
20.026
1.00
28.23

1443
CA
GLY
A
386
25.872
26.464
21.398
1.00
28.09

1444
C
GLY
A
386
26.927
27.539
21.582
1.00
28.17

1445
O
GLY
A
386
27.159
27.987
22.702
1.00
30.05

1446
N
ASP
A
387
27.555
27.965
20.490
1.00
29.00

1447
CA
ASP
A
387
28.602
28.982
20.555
1.00
29.78

1448
CB
ASP
A
387
29.691
28.690
19.520
1.00
33.93

1449
CG
ASP
A
387
30.174
27.263
19.569
1.00
37.57

1450
OD1
ASP
A
387
30.417
26.758
20.687
1.00
40.66

1451
OD2
ASP
A
387
30.320
26.651
18.489
1.00
39.44

1452
C
ASP
A
387
28.107
30.404
20.330
1.00
27.38

1453
O
ASP
A
387
28.889
31.348
20.396
1.00
27.02

1454
N
ARG
A
388
26.818
30.563
20.057
1.00
25.37

1455
CA
ARG
A
388
26.271
31.889
19.807
1.00
24.60

1456
CB
ARG
A
388
24.785
31.791
19.462
1.00
23.34

1457
CG
ARG
A
388
24.471
30.855
18.309
1.00
19.60

1458
CD
ARG
A
388
25.262
31.214
17.061
1.00
20.49

1459
NE
ARG
A
388
24.765
30.481
15.900
1.00
14.79

1460
CZ
ARG
A
388
25.332
30.498
14.700
1.00
16.61

1461
NH1
ARG
A
388
26.430
31.215
14.489
1.00
14.39

1462
NH2
ARG
A
388
24.798
29.789
13.714
1.00
14.57

1463
C
ARG
A
388
26.457
32.840
20.987
1.00
26.30

1464
O
ARG
A
388
26.286
32.458
22.143
1.00
26.77

1465
N
PRO
A
389
26.821
34.098
20.704
1.00
27.02

1466
CD
PRO
A
389
27.215
34.629
19.388
1.00
26.91

1467
CA
PRO
A
389
27.025
35.101
21.752
1.00
27.46

1468
CB
PRO
A
389
27.454
36.338
20.966
1.00
28.18

1469
CG
PRO
A
389
28.135
35.762
19.770
1.00
28.30

1470
C
PRO
A
389
25.739
35.352
22.539
1.00
28.08

1471
O
PRO
A
389
24.643
35.288
21.982
1.00
28.60

1472
N
GLY
A
390
25.881
35.620
23.834
1.00
27.99

1473
CA
GLY
A
390
24.731
35.912
24.674
1.00
27.31

1474
C
GLY
A
390
23.805
34.779
25.077
1.00
26.48

1475
O
GLY
A
390
22.720
35.038
25.601
1.00
25.44

1476
N
LEU
A
391
24.207
33.534
24.841
1.00
25.96

1477
CA
LEU
A
391
23.369
32.396
25.211
1.00
26.11

1478
CB
LEU
A
391
23.808
31.132
24.474
1.00
26.09

1479
CG
LEU
A
391
23.410
30.999
23.004
1.00
25.05

1480
OD1
LEU
A
391
24.037
29.734
22.431
1.00
23.61

1481
CD2
LEU
A
391
21.895
30.941
22.884
1.00
23.97

1482
C
LEU
A
391
23.430
32.135
26.708
1.00
27.86

1483
O
LEU
A
391
24.468
32.340
27.341
1.00
26.88

1484
N
LEU
A
392
22.318
31.662
27.260
1.00
28.14

1485
CA
LEU
A
392
22.230
31.366
28.682
1.00
31.00

1486
CB
LEU
A
392
20.863
31.794
29.225
1.00
30.68

1487
CG
LEU
A
392
20.575
31.444
30.690
1.00
32.59

1488
CD1
LEU
A
392
21.613
32.099
31.595
1.00
32.90

1489
CD2
LEU
A
392
19.173
31.906
31.057
1.00
31.69

1490
C
LEU
A
392
22.428
29.883
28.943
1.00
31.60

1491
O
LEU
A
392
23.371
29.471
29.618
1.00
33.05

1492
N
ASN
A
393
21.527
29.084
28.388
1.00
31.62

1493
CA
ASN
A
393
21.555
27.642
28.565
1.00
32.32

1494
CB
ASN
A
393
20.136
27.109
28.403
1.00
34.00

1495
CG
ASN
A
393
19.940
25.769
29.056
1.00
36.18

1496
OD1
ASN
A
393
18.821
25.265
29.121
1.00
38.80

1497
ND2
ASN
A
393
21.025
25.178
29.547
1.00
37.30

1498
C
ASN
A
393
22.501
26.938
27.586
1.00
31.82

1499
O
ASN
A
393
22.112
25.986
26.913
1.00
30.71

1500
N
VAL
A
394
23.743
27.406
27.526
1.00
31.16

1501
CA
VAL
A
394
24.748
26.838
26.634
1.00
31.48

1502
CB
VAL
A
394
26.140
27.467
26.912
1.00
31.26

1503
CG1
VAL
A
394
26.485
27.325
28.385
1.00
32.59

1504
CG2
VAL
A
394
27.204
26.802
26.049
1.00
31.72

1505
C
VAL
A
394
24.843
25.311
26.739
1.00
31.80

1506
O
VAL
A
394
24.984
24.619
25.728
1.00
32.39

1507
N
GLY
A
395
24.753
24.789
27.958
1.00
30.80

1508
CA
GLY
A
395
24.834
23.351
28.150
1.00
30.87

1509
C
GLY
A
395
23.747
22.558
27.443
1.00
31.11

1510
O
GLY
A
395
24.037
21.612
26.707
1.00
31.28

1511
N
HIS
A
396
22.493
22.940
27.662
1.00
30.39

1512
CA
HIS
A
396
21.370
22.248
27.047
1.00
30.64

1513
CB
HIS
A
396
20.046
22.779
27.613
1.00
33.97

1514
CG
HIS
A
396
19.864
22.503
29.077
1.00
38.64

1515
CD2
HIS
A
396
18.831
22.763
29.914
1.00
40.99

1516
ND1
HIS
A
396
20.841
21.913
29.849
1.00
39.58

1517
CE1
HIS
A
396
20.420
21.824
31.098
1.00
41.27

1518
NE2
HIS
A
396
19.204
22.334
31.165
1.00
41.61

1519
C
HIS
A
396
21.386
22.376
25.526
1.00
29.36

1520
O
HIS
A
396
20.970
21.465
24.821
1.00
28.36

1521
N
ILE
A
397
21.873
23.504
25.022
1.00
27.89

1522
CA
ILE
A
397
21.935
23.707
23.579
1.00
27.60

1523
CB
ILE
A
397
22.208
25.194
23.240
1.00
25.64

1524
CG2
ILE
A
397
22.465
25.366
21.743
1.00
25.46

1525
CG1
ILE
A
397
20.998
26.036
23.649
1.00
23.43

1526
CD1
ILE
A
397
21.234
27.535
23.573
1.00
23.81

1527
C
ILE
A
397
23.014
22.817
22.961
1.00
28.42

1528
O
ILE
A
397
22.837
22.292
21.863
1.00
28.52

1529
N
GLU
A
398
24.124
22.635
23.671
1.00
28.38

1530
CA
GLU
A
398
25.202
21.789
23.167
1.00
30.86

1531
CB
GLU
A
398
26.423
21.850
24.091
1.00
31.87

1532
CG
GLU
A
398
27.051
23.224
24.207
1.00
35.51

1533
CD
GLU
A
398
28.340
23.206
25.006
1.00
37.24

1534
OE1
GLU
A
398
28.347
22.630
26.114
1.00
38.47

1535
OE2
GLU
A
398
29.342
23.776
24.526
1.00
39.11

1536
C
GLU
A
398
24.743
20.339
23.037
1.00
30.96

1537
O
GLU
A
398
25.105
19.655
22.084
1.00
32.65

1538
N
LYS
A
399
23.950
19.870
23.996
1.00
31.74

1539
CA
LYS
A
399
23.457
18.495
23.966
1.00
32.12

1540
CB
LYS
A
399
22.721
18.166
25.272
1.00
34.57

1541
CG
LYS
A
399
21.269
18.617
25.317
1.00
37.40

1542
CD
LYS
A
399
20.332
17.512
24.854
1.00
39.89

1543
CE
LYS
A
399
19.038
18.078
24.284
1.00
40.38

1544
NZ
LYS
A
399
18.417
19.102
25.174
1.00
42.06

1545
C
LYS
A
399
22.522
18.335
22.770
1.00
30.88

1546
O
LYS
A
399
22.437
17.264
22.166
1.00
29.64

1547
N
MET
A
400
21.823
19.413
22.433
1.00
30.20

1548
CA
MET
A
400
20.909
19.408
21.298
1.00
30.04

1549
CB
MET
A
400
20.125
20.719
21.248
1.00
31.30

1550
CG
MET
A
400
18.626
20.562
21.377
1.00
34.42

1551
SD
MET
A
400
17.780
22.138
21.146
1.00
37.50

1552
CE
MET
A
400
17.589
22.649
22.799
1.00
35.32

1553
C
MET
A
400
21.705
19.251
20.006
1.00
28.14

1554
O
MET
A
400
21.406
18.386
19.177
1.00
27.06

1555
N
GLN
A
401
22.719
20.095
19.836
1.00
27.24

1556
CA
GLN
A
401
23.548
20.044
18.638
1.00
27.85

1557
CB
GLN
A
401
24.571
21.188
18.628
1.00
29.46

1558
CG
GLN
A
401
25.434
21.214
17.366
1.00
32.43

1559
CD
GLN
A
401
26.273
22.480
17.228
1.00
34.32

1560
CE1
GLN
A
401
27.074
22.809
18.102
1.00
34.44

1561
NE2
GLN
A
401
26.093
23.190
16.118
1.00
32.43

1562
C
GLN
A
401
24.269
18.705
18.539
1.00
27.48

1563
O
GLN
A
401
24.474
18.184
17.445
1.00
26.07

1564
N
GLU
A
402
24.641
18.149
19.687
1.00
27.34

1565
CA
GLU
A
402
25.334
16.865
19.729
1.00
28.25

1566
CB
GLU
A
402
25.617
16.464
21.184
1.00
30.37

1567
CO
GLU
A
402
26.263
15.089
21.339
1.00
35.80

1568
CD
GLU
A
402
26.573
14.744
22.787
1.00
38.57

1569
CE1
GLU
A
402
27.527
15.326
23.347
1.00
39.33

1570
OE2
GLU
A
402
25.856
13.895
23.365
1.00
39.79

1571
C
GLU
A
402
24.504
15.782
19.044
1.00
26.37

1572
O
GLU
A
402
25.017
15.030
18.216
1.00
26.12

1573
N
GLY
A
403
23.223
15.714
19.398
1.00
22.95

1574
CA
GLY
A
403
22.335
14.727
18.814
1.00
22.23

1575
C
GLY
A
403
22.119
14.941
17.326
1.00
22.14

1576
O
GLY
A
403
22.068
13.985
16.553
1.00
22.69

1577
N
ILE
A
404
21.991
16.199
16.918
1.00
20.27

1578
CA
ILE
A
404
21.790
16.528
15.508
1.00
20.28

1579
CB
ILE
A
404
21.501
18.047
15.333
1.00
18.92

1580
CG2
ILE
A
404
21.570
18.439
13.853
1.00
18.08

1581
CG1
ILE
A
404
20.130
18.370
15.931
1.00
20.64

1582
CD1
ILE
A
404
19.754
19.853
15.927
1.00
21.12

1583
C
ILE
A
404
23.012
16.129
14.683
1.00
20.45

1584
O
ILE
A
404
22.885
15.494
13.634
1.00
19.39

1585
N
VAL
A
405
24.195
16.491
15.170
1.00
22.04

1586
CA
VAL
A
405
25.441
16.167
14.484
1.00
24.01

1587
CB
VAL
A
405
26.654
16.764
15.229
1.00
24.63

1588
CG1
VAL
A
405
27.950
16.264
14.608
1.00
26.70

1589
CG2
VAL
A
405
26.597
18.282
15.168
1.00
25.08

1590
C
VAL
A
405
25.623
14.656
14.376
1.00
24.35

1591
O
VAL
A
405
26.062
14.145
13.347
1.00
24.50

1592
N
HIS
A
406
25.286
13.951
15.451
1.00
24.73

1593
CA
HIS
A
406
25.393
12.499
15.494
1.00
25.40

1594
CB
HIS
A
406
24.870
11.980
16.834
1.00
27.91

1595
CG
HIS
A
406
24.719
10.492
16.890
1.00
29.97

1596
CD2
HIS
A
406
23.623
9.704
16.779
1.00
31.72

1597
ND1
HIS
A
406
25.790
9.638
17.041
1.00
32.64

1598
CE1
HIS
A
406
25.362
8.388
17.020
1.00
31.24

1599
NE2
HIS
A
406
24.051
8.400
16.861
1.00
32.29

1600
C
HIS
A
406
24.573
11.891
14.362
1.00
24.78

1601
O
HIS
A
406
25.073
11.085
13.573
1.00
23.70

1602
N
VAL
A
407
23.306
12.287
14.297
1.00
24.16

1603
CA
VAL
A
407
22.394
11.797
13.276
1.00
24.60

1604
CB
VAL
A
407
20.962
12.319
13.536
1.00
26.47

1605
CG1
VAL
A
407
20.059
12.000
12.360
1.00
29.88

1606
CG2
VAL
A
407
20.412
11.675
14.805
1.00
27.86

1607
C
VAL
A
407
22.872
12.218
11.885
1.00
23.32

1608
O
VAL
A
407
22.752
11.455
10.922
1.00
21.28

1609
N
LEU
A
408
23.430
13.422
11.785
1.00
21.40

1610
CA
LEU
A
408
23.939
13.914
10.510
1.00
20.88

1611
CB
LEU
A
408
24.388
15.378
10.636
1.00
20.25

1612
CG
LEU
A
408
25.166
15.976
9.458
1.00
19.60

1613
CD1
LEU
A
408
24.324
15.912
8.188
1.00
18.77

1614
CD2
LEU
A
408
25.545
17.412
9.770
1.00
20.66

1615
C
LEU
A
408
25.108
13.058
10.026
1.00
21.76

1616
O
LEU
A
408
25.145
12.653
8.867
1.00
21.23

1617
N
ARG
A
409
26.057
12.776
10.917
1.00
22.31

1618
CA
ARG
A
409
27.217
11.971
10.547
1.00
23.13

1619
CB
ARG
A
409
28.170
11.788
11.736
1.00
25.75

1620
CG
ARG
A
409
29.480
11.102
11.332
1.00
30.84

1621
CD
ARG
A
409
30.361
10.722
12.517
1.00
34.64

1622
NE
ARG
A
409
30.566
11.828
13.444
1.00
36.72

1623
CZ
ARG
A
409
29.936
11.949
14.607
1.00
38.12

1624
NH1
ARG
A
409
29.063
11.027
14.986
1.00
40.03

1625
NH2
ARG
A
409
30.175
12.993
15.390
1.00
40.43

1626
C
ARG
A
409
26.800
10.598
10.039
1.00
23.39

1627
O
ARG
A
409
27.345
10.093
9.056
1.00
22.61

1628
N
LEU
A
410
25.835
9.991
10.718
1.00
22.60

1629
CA
LEU
A
410
25.351
8.673
10.332
1.00
24.37

1630
CB
LEU
A
410
24.452
8.106
11.438
1.00
24.59

1631
CC
LEU
A
410
25.217
7.686
12.701
1.00
27.68

1632
CD1
LEU
A
410
24.251
7.309
13.813
1.00
27.24

1633
CD2
LEU
A
410
26.133
6.519
12.366
1.00
26.90

1634
C
LEU
A
410
24.595
8.737
9.007
1.00
23.58

1635
O
LEU
A
410
24.750
7.870
8.143
1.00
22.71

1636
N
HIS
A
411
23.786
9.776
8.844
1.00
22.55

1637
CA
HIS
A
411
23.015
9.944
7.618
1.00
22.81

1638
CB
HIS
A
411
22.097
11.168
7.741
1.00
22.24

1639
CG
HIS
A
411
21.156
11.337
6.590
1.00
22.11

1640
CD2
HIS
A
411
19.946
10.782
6.342
1.00
23.05

1641
ND1
HIS
A
411
21.437
12.140
5.505
1.00
23.65

1642
CE1
HIS
A
411
20.441
12.074
4.639
1.00
20.84

1643
NE2
HIS
A
411
19.524
11.256
5.122
1.00
24.45

1644
C
HIS
A
411
23.933
10.092
6.406
1.00
22.74

1645
O
HIS
A
411
23.689
9.497
5.351
1.00
21.42

1646
N
LEU
A
412
24.990
10.886
6.555
1.00
20.60

1647
CA
LEU
A
412
25.931
11.093
5.460
1.00
22.09

1648
CB
LEU
A
412
26.972
12.151
5.838
1.00
21.12

1649
CG
LEU
A
412
26.441
13.576
6.011
1.00
20.72

1650
OD1
LEU
A
412
27.572
14.496
6.451
1.00
20.64

1651
OD2
LEU
A
412
25.828
14.060
4.693
1.00
21.54

1652
C
LEU
A
412
26.640
9.806
5.063
1.00
22.50

1653
O
LEU
A
412
26.921
9.587
3.886
1.00
22.76

1654
N
GLN
A
413
26.944
8.960
6.041
1.00
24.45

1655
CA
GLN
A
413
27.622
7.702
5.748
1.00
26.41

1656
CB
GLN
A
413
28.021
6.987
7.043
1.00
28.87

1657
OG
GLN
A
413
29.245
7.579
7.714
1.00
32.50

1658
CD
GLN
A
413
30.154
6.519
8.306
1.00
35.70

1659
OE1
GLN
A
413
29.809
5.862
9.286
1.00
36.19

1660
NE2
GLN
A
413
31.326
6.343
7.702
1.00
38.34

1661
C
GLN
A
413
26.765
6.775
4.889
1.00
26.96

1662
O
GLN
A
413
27.271
6.120
3.976
1.00
26.69

1663
N
SER
A
414
25.467
6.729
5.173
1.00
26.98

1664
CA
SER
A
414
24.555
5.877
4.417
1.00
27.71

1665
CB
SER
A
414
23.380
5.452
5.300
1.00
29.19

1666
OG
SER
A
414
22.560
6.558
5.632
1.00
33.45

1667
C
SER
A
414
24.017
6.521
3.138
1.00
26.94

1668
O
SER
A
414
23.709
5.820
2.175
1.00
27.54

1669
N
ASN
A
415
23.901
7.848
3.122
1.00
25.54

1670
CA
ASN
A
415
23.377
8.552
1.947
1.00
24.76

1671
CB
ASN
A
415
22.679
9.853
2.377
1.00
24.73

1672
CG
ASN
A
415
21.714
10.390
1.317
1.00
26.54

1673
OD1
ASN
A
415
21.324
11.562
1.350
1.00
25.37

1674
ND2
ASN
A
415
21.310
9.529
0.386
1.00
24.83

1675
C
ASN
A
415
24.472
8.870
0.927
1.00
24.23

1676
O
ASN
A
415
24.202
8.951
−0.271
1.00
23.51

1677
N
HIS
A
416
25.704
9.053
1.403
1.00
23.19

1678
CA
HIS
A
416
26.837
9.354
0.526
1.00
24.23

1679
CB
HIS
A
416
27.273
10.820
0.674
1.00
22.51

1680
CG
HIS
A
416
26.236
11.811
0.239
1.00
21.91

1681
CD2
HIS
A
416
25.999
12.381
−0.967
1.00
19.28

1682
ND1
HIS
A
416
25.279
12.314
1.094
1.00
22.80

1683
CE1
HIS
A
416
24.497
13.152
0.434
1.00
17.33

1684
NE2
HIS
A
416
24.912
13.210
−0.819
1.00
20.76

1685
C
HIS
A
416
28.019
8.445
0.859
1.00
26.11

1686
O
HIS
A
416
29.076
8.912
1.285
1.00
24.94

1687
N
PRO
A
417
27.859
7.131
0.647
1.00
29.11

1688
CD
PRO
A
417
26.708
6.470
0.007
1.00
29.49

1689
CA
PRO
A
417
28.920
6.163
0.935
1.00
30.85

1690
CB
PRO
A
417
28.241
4.824
0.656
1.00
31.26

1691
CG
PRO
A
417
27.314
5.162
−0.472
1.00
30.77

1692
C
PRO
A
417
30.193
6.350
0.118
1.00
33.62

1693
O
PRO
A
417
31.264
5.895
0.524
1.00
35.12

1694
N
ASP
A
418
30.084
7.019
−1.025
1.00
34.60

1695
CA
ASP
A
418
31.247
7.230
−1.874
1.00
36.67

1696
CB
ASP
A
418
30.832
7.265
−3.349
1.00
39.63

1697
CG
ASP
A
418
30.147
5.981
−3.794
1.00
41.06

1698
OD1
ASP
A
418
30.576
4.893
−3.352
1.00
42.57

1699
OD2
ASP
A
418
29.188
6.058
−4.592
1.00
43.11

1700
C
ASP
A
418
32.048
8.483
−1.541
1.00
37.42

1701
O
ASP
A
418
33.252
8.534
−1.802
1.00
37.62

1702
N
ASP
A
419
31.399
9.492
−0.966
1.00
37.02

1703
CA
ASP
A
419
32.118
10.715
−0.632
1.00
37.69

1704
CB
ASP
A
419
31.185
11.909
−0.446
1.00
36.87

1705
CG
ASP
A
419
31.953
13.225
−0.346
1.00
37.47

1706
OD1
ASP
A
419
33.059
13.232
0.238
1.00
36.42

1707
OD2
ASP
A
419
31.455
14.253
−0.845
1.00
37.98

1708
C
ASP
A
419
32.953
10.566
0.620
1.00
38.20

1709
O
ASP
A
419
32.444
10.440
1.736
1.00
37.99

1710
N
ILE
A
420
34.255
10.612
0.399
1.00
39.15

1711
CA
ILE
A
420
35.263
10.494
1.429
1.00
37.95

1712
CB
ILE
A
420
36.621
10.896
0.829
1.00
39.91

1713
CG2
ILE
A
420
37.041
9.869
−0.219
1.00
40.60

1714
CG1
ILE
A
420
36.499
12.270
0.150
1.00
41.10

1715
CD1
ILE
A
420
37.772
12.762
−0.510
1.00
42.96

1716
C
ILE
A
420
35.022
11.292
2.716
1.00
35.07

1717
O
ILE
A
420
34.524
10.764
3.711
1.00
35.43

1718
N
PHE
A
421
35.380
12.568
2.685
1.00
31.63

1719
CA
PHE
A
421
35.264
13.435
3.846
1.00
26.48

1720
CB
PHE
A
421
36.496
14.341
3.943
1.00
29.04

1721
CG
PHE
A
421
37.809
13.614
3.925
1.00
30.93

1722
OD1
PHE
A
421
38.353
13.160
2.733
1.00
33.42

1723
CD2
PHE
A
421
38.524
13.423
5.100
1.00
31.75

1724
CE1
PHE
A
421
39.599
12.529
2.709
1.00
34.29

1725
CE2
PHE
A
421
39.768
12.794
5.089
1.00
31.88

1726
CZ
PHE
A
421
40.306
12.348
3.892
1.00
33.09

1727
C
PHE
A
421
34.039
14.339
3.827
1.00
23.47

1728
O
PHE
A
421
34.156
15.505
4.176
1.00
21.09

1729
N
LEU
A
422
32.869
13.832
3.449
1.00
20.27

1730
CA
LEU
A
422
31.704
14.715
3.403
1.00
17.44

1731
CB
LEU
A
422
30.476
13.972
2.851
1.00
15.99

1732
CG
LEU
A
422
29.237
14.847
2.598
1.00
14.82

1733
CD1
LEU
A
422
29.607
16.092
1.808
1.00
15.78

1734
CD2
LEU
A
422
28.190
14.039
1.867
1.00
16.91

1735
C
LEU
A
422
31.376
15.381
4.745
1.00
17.17

1736
O
LEU
A
422
30.989
16.561
4.784
1.00
15.16

1737
N
PHE
A
423
31.537
14.656
5.850
1.00
15.85

1738
CA
PHE
A
423
31.242
15.247
7.154
1.00
15.61

1739
CB
PHE
A
423
31.333
14.189
8.264
1.00
17.14

1740
CG
PHE
A
423
30.974
14.708
9.626
1.00
18.64

1741
CD1
PHE
A
423
29.698
15.202
9.888
1.00
20.33

1742
CD2
PHE
A
423
31.910
14.705
10.651
1.00
20.31

1743
CE1
PHE
A
423
29.360
15.685
11.157
1.00
20.29

1744
CE2
PHE
A
423
31.583
15.186
11.924
1.00
21.44

1745
GZ
PHE
A
423
30.305
15.676
12.175
1.00
22.31

1746
C
PHE
A
423
32.194
16.416
7.451
1.00
16.28

1747
O
PI1E
A
423
31.750
17.537
7.727
1.00
14.24

1748
N
PRO
A
424
33.519
16.174
7.416
1.00
17.45

1749
CD
PRO
A
424
34.280
14.915
7.331
1.00
17.91

1750
CA
PRO
A
424
34.397
17.313
7.697
1.00
16.84

1751
CB
PRO
A
424
35.797
16.680
7.749
1.00
19.13

1752
CG
PRO
A
424
35.657
15.406
6.971
1.00
18.96

1753
C
PRO
A
424
34.255
18.437
6.657
1.00
15.92

1754
O
PRO
A
424
34.467
19.610
6.966
1.00
15.44

1755
N
LYS
A
425
33.882
18.086
5.428
1.00
16.05

1756
CA
LYS
A
425
33.680
19.100
4.396
1.00
15.22

1757
CB
LYS
A
425
33.268
18.456
3.068
1.00
15.46

1758
CG
LYS
A
425
34.373
17.716
2.332
1.00
16.19

1759
CD
LYS
A
425
33.824
17.126
1.044
1.00
17.44

1760
CE
LYS
A
425
34.866
16.327
0.278
1.00
19.89

1761
NZ
LYS
A
425
34.278
15.771
−0.982
1.00
18.37

1762
C
LYS
A
425
32.561
20.034
4.850
1.00
14.66

1763
O
LYS
A
425
32.654
21.259
4.712
1.00
13.26

1764
N
LEU
A
426
31.497
19.445
5.394
1.00
13.97

1765
CA
LEU
A
426
30.351
20.219
5.864
1.00
14.01

1766
CB
LEU
A
426
29.155
19.301
6.136
1.00
14.60

1767
CG
LEU
A
426
28.490
18.720
4.887
1.00
18.11

1768
CD1
LEU
A
426
27.366
17.777
5.289
1.00
19.14

1769
CD2
LEU
A
426
27.948
19.859
4.027
1.00
19.11

1770
C
LEU
A
426
30.694
21.025
7.110
1.00
15.51

1771
O
LEU
A
426
30.200
22.138
7.290
1.00
16.69

1772
N
LEU
A
427
31.546
20.477
7.971
1.00
16.13

1773
CA
LEU
A
427
31.948
21.221
9.159
1.00
17.20

1774
CB
LEU
A
427
32.875
20.386
10.048
1.00
19.20

1775
CG
LEU
A
427
32.221
19.176
10.725
1.00
21.00

1776
CD1
LEU
A
427
33.248
18.435
11.574
1.00
22.86

1777
CD2
LEU
A
427
31.055
19.637
11.584
1.00
22.35

1778
C
LEU
A
427
32.669
22.480
8.691
1.00
17.44

1779
O
LEU
A
427
32.495
23.556
9.266
1.00
15.95

1780
N
GLN
A
428
33.480
22.357
7.643
1.00
16.16

1781
CA
GLN
A
428
34.183
23.532
7.134
1.00
16.84

1782
CB
GLN
A
428
35.235
23.150
6.087
1.00
17.05

1783
CG
GLN
A
428
36.001
24.372
5.560
1.00
20.71

1784
CD
GLN
A
428
36.981
24.039
4.453
1.00
22.77

1785
OE1
GLN
A
428
36.625
23.398
3.468
1.00
25.06

1786
NE2
GLN
A
428
38.224
24.488
4.606
1.00
26.03

1787
C
GLN
A
428
33.179
24.512
6.525
1.00
17.18

1788
O
GLN
A
428
33.333
25.728
6.656
1.00
17.33

1789
N
LYS
A
429
32.147
23.995
5.859
1.00
17.54

1790
CA
LYS
A
429
31.132
24.871
5.261
1.00
17.07

1791
CB
LYS
A
429
30.077
24.061
4.505
1.00
17.70

1792
CG
LYS
A
429
30.611
23.303
3.312
1.00
19.51

1793
CD
LYS
A
429
31.331
24.217
2.336
1.00
22.06

1794
CE
LYS
A
429
31.888
23.424
1.151
1.00
22.64

1795
NZ
LYS
A
429
32.800
24.262
0.326
1.00
21.64

1796
C
LYS
A
429
30.441
25.712
6.327
1.00
18.54

1797
O
LYS
A
429
30.070
26.865
6.079
1.00
16.97

1798
N
MET
A
430
30.258
25.136
7.513
1.00
18.74

1799
CA
MET
A
430
29.621
25.868
8.599
1.00
19.35

1800
CB
MET
A
430
29.418
24.957
9.810
1.00
22.86

1801
CO
MET
A
430
28.556
23.742
9.505
1.00
25.60

1802
SD
MET
A
430
28.185
22.755
10.953
1.00
29.86

1803
CE
MET
A
430
26.648
23.513
11.472
1.00
30.44

1804
C
MET
A
430
30.509
27.050
8.977
1.00
19.48

1805
O
MET
A
430
30.017
28.142
9.238
1.00
17.93

1806
N
ALA
A
431
31.819
26.824
9.010
1.00
19.56

1807
CA
ALA
A
431
32.768
27.883
9.345
1.00
18.57

1808
CB
ALA
A
431
34.160
27.293
9.551
1.00
20.87

1809
C
ALA
A
431
32.800
28.931
8.236
1.00
19.19

1810
O
ALA
A
431
32.910
30.136
8.498
1.00
18.72

1811
N
ASP
A
432
32.711
28.471
6.992
1.00
17.33

1812
CA
ASP
A
432
32.719
29.382
5.854
1.00
17.47

1813
CB
ASP
A
432
32.751
28.608
4.537
1.00
18.81

1814
CG
ASP
A
432
34.086
27.928
4.285
1.00
22.11

1815
OD1
ASP
A
432
35.085
28.306
4.925
1.00
23.74

1816
OD2
ASP
A
432
34.136
27.026
3.426
1.00
23.76

1817
C
ASP
A
432
31.477
30.268
5.890
1.00
17.16

1818
O
ASP
A
432
31.542
31.454
5.563
1.00
16.05

1819
N
LEU
A
433
30.349
29.691
6.296
1.00
15.92

1820
CA
LEU
A
433
29.097
30.442
6.367
1.00
15.51

1821
CB
LEU
A
433
27.919
29.500
6.645
1.00
14.97

1822
CG
LEU
A
433
27.457
28.645
5.461
1.00
16.25

1823
OD1
LBU
A
433
26.435
27.633
5.928
1.00
15.43

1824
CD2
LEU
A
433
26.852
29.532
4.379
1.00
16.30

1825
C
LEU
A
433
29.148
31.523
7.436
1.00
16.51

1826
O
LEU
A
433
28.643
32.623
7.240
1.00
15.91

1827
N
ARG
A
434
29.756
31.207
8.573
1.00
17.51

1828
CA
ARG
A
434
29.857
32.181
9.651
1.00
19.49

1829
CB
ARG
A
434
30.546
31.554
10.863
1.00
20.19

1830
CG
ARG
A
434
30.526
32.444
12.094
1.00
24.32

1831
CD
ARG
A
434
30.936
31.678
13.331
1.00
27.77

1832
NE
ARG
A
434
29.962
30.650
13.689
1.00
30.42

1833
CZ
ARG
A
434
30.013
29.949
14.816
1.00
32.49

1834
NH1
ARG
A
434
30.992
30.171
15.682
1.00
33.93

1835
NH2
ARG
A
434
29.086
29.037
15.086
1.00
32.62

1836
C
ARG
A
434
30.644
33.397
9.162
1.00
19.24

1837
O
ARG
A
434
30.275
34.539
9.432
1.00
20.11

1838
N
GLN
A
435
31.730
33.145
8.441
1.00
20.35

1839
CA
GLN
A
435
32.554
34.224
7.905
1.00
21.41

1840
CB
GLN
A
435
33.828
33.656
7.272
1.00
23.62

1841
CG
GLN
A
435
34.616
34.659
6.435
1.00
28.57

1842
CD
GLN
A
435
35.501
35.574
7.260
1.00
33.29

1843
OE1
GLN
A
435
35.091
36.091
8.301
1.00
36.07

1844
NE2
GLN
A
435
36.725
35.789
6.788
1.00
36.08

1845
C
GLN
A
435
31.757
34.987
6.852
1.00
20.82

1846
O
GLN
A
435
31.773
36.217
6.814
1.00
19.43

1847
N
LEU
A
436
31.058
34.244
5.999
1.00
19.72

1848
CA
LEU
A
436
30.251
34.842
4.945
1.00
18.86

1849
CB
LEU
A
436
29.571
33.742
4.121
1.00
18.95

1850
CG
LEU
A
436
28.865
34.160
2.829
1.00
20.08

1851
CD1
LEU
A
436
29.911
34.595
1.800
1.00
20.86

1852
CD2
LEU
A
436
28.053
32.982
2.281
1.00
21.90

1853
C
LBU
A
436
29.187
35.783
5.525
1.00
18.74

1854
O
LEU
A
436
28.905
36.838
4.951
1.00
17.29

1855
N
VAL
A
437
28.592
35.401
6.655
1.00
17.24

1856
CA
VAL
A
437
27.561
36.235
7.283
1.00
17.47

1857
CB
VAL
A
437
26.774
35.456
8.361
1.00
17.76

1858
CG1
VAL
A
437
25.846
36.405
9.120
1.00
18.67

1859
CG2
VAL
A
437
25.945
34.348
7.700
1.00
14.52

1860
C
VAL
A
437
28.170
37.478
7.928
1.00
18.46

1861
O
VAL
A
437
27.615
38.576
7.834
1.00
18.68

1862
N
THR
A
438
29.309
37.301
8.588
1.00
18.45

1863
CA
THR
A
438
29.984
38.418
9.237
1.00
19.82

1864
CB
THR
A
438
31.316
37.969
9.877
1.00
20.76

1865
OG1
THR
A
438
31.058
36.955
10.856
1.00
22.73

1866
CG2
THR
A
438
32.006
39.146
10.551
1.00
23.28

1867
C
THR
A
438
30.271
39.498
8.204
1.00
20.08

1868
O
THR
A
438
30.034
40.685
8.440
1.00
20.49

1869
N
GLU
A
439
30.778
39.071
7.052
1.00
18.53

1870
CA
GLU
A
439
31.104
39.983
5.972
1.00
19.18

1871
CB
GLU
A
439
31.900
39.236
4.897
1.00
19.51

1872
CG
GLU
A
439
33.061
38.440
5.491
1.00
23.78

1873
CD
GLU
A
439
33.912
37.735
4.455
1.00
25.56

1874
OE1
GLU
A
439
33.347
37.165
3.502
1.00
27.66

1875
OE2
GLU
A
439
35.152
37.738
4.607
1.00
27.05

1876
C
GLU
A
439
29.852
40.617
5.369
1.00
17.55

1877
O
GLU
A
439
29.862
41.786
4.988
1.00
18.18

1878
N
HIS
A
440
28.774
39.843
5.279
1.00
16.47

1879
CA
HIS
A
440
27.527
40.353
4.725
1.00
15.35

1880
CB
HIS
A
440
26.512
39.217
4.561
1.00
13.45

1881
CG
HIS
A
440
25.169
39.663
4.063
1.00
13.44

1882
CD2
HIS
A
440
24.005
39.879
4.719
1.00
14.46

1883
ND1
HIS
A
440
24.913
39.927
2.734
1.00
14.54

1884
CE1
HIS
A
440
23.649
40.284
2.593
1.00
14.39

1885
NE2
HIS
A
440
23.076
40.265
3.783
1.00
14.22

1886
C
HIS
A
440
26.947
41.444
5.627
1.00
15.34

1887
O
HIS
A
440
26.494
42.474
5.139
1.00
16.88

1888
N
ALA
A
441
26.956
41.216
6.936
1.00
16.12

1889
CA
ALA
A
441
26.425
42.197
7.879
1.00
17.96

1890
CB
ALA
A
441
26.513
41.661
9.305
1.00
17.75

1891
C
ALA
A
441
27.190
43.518
7.773
1.00
19.46

1892
O
ALA
A
441
26.619
44.594
7.956
1.00
18.94

1893
N
GLN
A
442
28.483
43.431
7.479
1.00
21.32

1894
CA
GLN
A
442
29.309
44.630
7.348
1.00
22.42

1895
CB
GLN
A
442
30.781
44.255
7.158
1.00
26.37

1896
CG
GLN
A
442
31.717
45.455
7.074
1.00
31.72

1897
CD
GLN
A
442
33.178
45.053
6.974
1.00
34.48

1898
OE1
GLN
A
442
33.675
44.272
7.786
1.00
37.93

1899
NE2
GLN
A
442
33.874
45.588
5.979
1.00
35.81

1900
C
GLN
A
442
28.831
45.449
6.157
1.00
21.76

1901
O
GLN
A
442
28.707
46.670
6.240
1.00
20.34

1902
N
LEU
A
443
28.557
44.771
5.047
1.00
19.43

1903
CA
LEU
A
443
28.087
45.452
3.851
1.00
20.58

1904
CB
LEU
A
443
28.060
44.491
2.661
1.00
21.26

1905
CG
LEU
A
443
27.571
45.092
1.339
1.00
23.72

1906
CD1
LEU
A
443
28.492
46.244
0.924
1.00
23.27

1907
CD2
LEU
A
443
27.542
44.016
0.268
1.00
23.43

1908
C
LEU
A
443
26.690
46.012
4.100
1.00
19.34

1909
O
LEU
A
443
26.373
47.114
3.663
1.00
20.88

1910
N
VAL
A
444
25.859
45.250
4.808
1.00
19.86

1911
CA
VAL
A
444
24.504
45.693
5.119
1.00
19.89

1912
CB
VAL
A
444
23.723
44.615
5.918
1.00
21.23

1913
CG1
VAL
A
444
22.357
45.155
6.342
1.00
22.52

1914
CG2
VAL
A
444
23.536
43.370
5.058
1.00
20.41

1915
C
VAL
A
444
24.557
46.992
5.928
1.00
21.15

1916
O
VAL
A
444
23.755
47.897
5.710
1.00
20.95

1917
N
GLN
A
445
25.512
47.083
6.849
1.00
21.46

1918
CA
GLN
A
445
25.663
48.278
7.672
1.00
23.89

1919
CB
GLN
A
445
26.722
48.047
8.752
1.00
27.62

1920
CG
GLN
A
445
26.863
49.191
9.753
1.00
32.28

1921
CD
GLN
A
445
25.636
49.366
10.638
1.00
35.43

1922
OE1
GLN
A
445
25.623
50.212
11.533
1.00
38.17

1923
NE2
GLN
A
445
24.602
48.567
10.395
1.00
37.92

1924
C
GLN
A
445
26.059
49.469
6.797
1.00
24.56

1925
O
GLN
A
445
25.586
50.588
7.003
1.00
22.97

1926
N
ILE
A
446
26.931
49.222
5.823
1.00
23.13

1927
CA
ILE
A
446
27.378
50.271
4.915
1.00
24.75

1928
CB
ILE
A
446
28.475
49.747
3.958
1.00
24.82

1929
CG2
ILE
A
446
28.747
50.759
2.855
1.00
24.01

1930
CG1
ILE
A
446
29.753
49.461
4.753
1.00
25.40

1931
CD1
ILE
A
446
30.852
48.807
3.946
1.00
25.53

1932
C
ILE
A
446
26.194
50.780
4.099
1.00
25.90

1933
O
ILE
A
446
25.990
51.989
3.968
1.00
26.44

1934
N
ILE
A
447
25.413
49.850
3.552
1.00
26.77

1935
CA
ILE
A
447
24.236
50.201
2.766
1.00
29.88

1936
CB
ILE
A
447
23.539
48.937
2.213
1.00
30.75

1937
CG2
ILE
A
447
22.150
49.299
1.663
1.00
33.39

1938
CG1
ILE
A
447
24.407
48.307
1.121
1.00
31.69

1939
CD1
ILE
A
447
23.811
47.036
0.510
1.00
34.09

1940
C
ILE
A
447
23.248
50.979
3.634
1.00
30.49

1941
O
ILE
A
447
22.670
51.979
3.206
1.00
30.43

1942
N
LYS
A
448
23.095
50.538
4.873
1.00
32.72

1943
CA
LYS
A
448
22.175
51.166
5.807
1.00
36.04

1944
CB
LYS
A
448
22.169
50.377
7.121
1.00
37.66

1945
CG
LYS
A
448
21.205
50.919
8.162
1.00
40.69

1946
CD
LYS
A
448
20.930
49.888
9.229
1.00
41.72

1947
CE
LYS
A
448
19.933
50.405
10.241
1.00
44.25

1948
NZ
LYS
A
448
20.486
51.487
11.103
1.00
45.65

1949
C
LYS
A
448
22.480
52.634
6.093
1.00
36.68

1950
O
LYS
A
448
21.566
53.450
6.206
1.00
36.26

1951
N
LYS
A
449
23.759
52.977
6.203
1.00
37.99

1952
CA
LYS
A
449
24.129
54.358
6.495
1.00
39.24

1953
CB
LYS
A
449
25.330
54.395
7.450
1.00
41.14

1954
CG
LYS
A
449
26.685
54.357
6.757
1.00
43.28

1955
CD
LYS
A
449
27.829
54.400
7.765
1.00
44.36

1956
CE
LYS
A
449
27.939
53.086
8.518
1.00
45.26

1957
NZ
LYS
A
449
28.212
51.958
7.586
1.00
44.67

1958
C
LYS
A
449
24.449
55.179
5.246
1.00
39.55

1959
O
LYS
A
449
24.523
56.408
5.307
1.00
39.79

1960
N
THR
A
450
24.630
54.502
4.117
1.00
39.02

1961
CA
THR
A
450
24.962
55.175
2.865
1.00
39.78

1962
CB
THR
A
450
26.150
54.462
2.168
1.00
40.83

1963
OG1
THR
A
450
27.381
54.930
2.736
1.00
41.96

1964
CG2
THR
A
450
26.149
54.722
0.671
1.00
42.44

1965
C
THR
A
450
23.802
55.298
1.879
1.00
39.33

1966
O
THR
A
450
23.724
56.263
1.120
1.00
39.15

1967
N
GLU
A
451
22.903
54.323
1.888
1.00
38.93

1968
CA
GLU
A
451
21.765
54.341
0.979
1.00
39.36

1969
CB
GLU
A
451
21.601
52.971
0.309
1.00
37.13

1970
CG
GLU
A
451
22.786
52.508
−0.542
1.00
33.20

1971
CD
GLU
A
451
22.987
53.336
−1.801
1.00
31.38

1972
OE1
GLU
A
451
21.993
53.869
−2.338
1.00
31.23

1973
OE2
GLU
A
451
24.140
53.436
−2.269
1.00
27.05

1974
C
GLU
A
451
20.480
54.701
1.718
1.00
41.61

1975
O
GLU
A
451
19.787
53.825
2.235
1.00
41.95

1976
N
SER
A
452
20.166
55.991
1.771
1.00
44.12

1977
CA
SER
A
452
18.955
56.445
2.444
1.00
46.91

1978
CB
SER
A
452
19.066
57.928
2.804
1.00
47.79

1979
OG
SER
A
452
20.074
58.140
3.781
1.00
49.02

1980
C
SER
A
452
17.767
56.216
1.521
1.00
48.12

1981
O
SER
A
452
16.611
56.306
1.933
1.00
48.49

1982
N
ASP
A
453
18.077
55.920
0.264
1.00
49.25

1983
CA
ASP
A
453
17.068
55.654
−0.750
1.00
50.01

1984
CB
ASP
A
453
17.754
55.278
−2.063
1.00
51.19

1985
CG
ASP
A
453
19.029
54.482
−1.845
1.00
51.21

1986
OD1
ASP
A
453
19.964
55.027
−1.223
1.00
52.21

1987
OD2
ASP
A
453
19.100
53.317
−2.288
1.00
52.20

1988
C
ASP
A
453
16.174
54.516
−0.287
1.00
49.54

1989
O
ASP
A
453
14.965
54.524
−0.513
1.00
50.36

1990
N
ALA
A
454
16.786
53.537
0.367
1.00
49.32

1991
CA
ALA
A
454
16.069
52.382
0.877
1.00
47.69

1992
CB
ALA
A
454
16.179
51.241
−0.102
1.00
48.66

1993
C
ALA
A
454
16.668
51.988
2.222
1.00
46.49

1994
O
ALA
A
454
17.885
51.940
2.373
1.00
47.87

1995
N
ALA
A
455
15.807
51.707
3.195
1.00
43.89

1996
CA
ALA
A
455
16.250
51.340
4.533
1.00
41.22

1997
CB
ALA
A
455
15.306
51.944
5.568
1.00
41.01

1998
C
ALA
A
455
16.341
49.829
4.724
1.00
39.82

1999
O
ALA
A
455
17.060
49.146
3.990
1.00
41.52

2000
N
LEU
A
456
15.625
49.329
5.728
1.00
36.01

2001
CA
LEU
A
456
15.580
47.904
6.063
1.00
32.30

2002
CB
LEU
A
456
16.744
47.508
6.981
1.00
33.09

2003
CG
LEU
A
456
18.083
47.052
6.390
1.00
33.05

2004
CD1
LEU
A
456
18.977
46.576
7.525
1.00
32.55

2005
CD2
LEU
A
456
17.870
45.925
5.391
1.00
31.55

2006
C
LEU
A
456
14.272
47.560
6.769
1.00
29.76

2007
O
LEU
A
456
13.758
48.345
7.574
1.00
26.72

2008
N
HIS
A
457
13.745
46.378
6.465
1.00
26.87

2009
CA
HIS
A
457
12.505
45.897
7.061
1.00
25.80

2010
CB
HIS
A
457
12.113
44.558
6.421
1.00
24.73

2011
CG
HIS
A
457
10.846
43.968
6.963
1.00
25.28

2012
CD2
HIS
A
457
10.567
43.401
8.160
1.00
24.58

2013
ND1
HIS
A
457
9.680
43.901
6.229
1.00
26.52

2014
CE1
HIS
A
457
8.740
43.316
6.950
1.00
25.66

2015
NE2
HIS
A
457
9.253
43.003
8.127
1.00
26.42

2016
C
HIS
A
457
12.711
45.716
8.567
1.00
25.90

2017
O
HIS
A
457
13.794
45.331
9.012
1.00
25.20

2018
N
PRO
A
458
11.669
45.995
9.368
1.00
25.60

2019
CD
PRO
A
458
10.368
46.543
8.941
1.00
26.08

2020
CA
PRO
A
458
11.719
45.868
10.829
1.00
25.42

2021
CB
PRO
A
458
10.257
46.032
11.229
1.00
25.91

2022
CG
PRO
A
458
9.777
47.043
10.243
1.00
27.38

2023
C
PRO
A
458
12.314
44.557
11.342
1.00
25.07

2024
O
PRO
A
458
13.151
44.559
12.246
1.00
25.29

2025
N
LEU
A
459
11.878
43.436
10.775
1.00
23.71

2026
CA
LEU
A
459
12.383
42.141
11.214
1.00
22.76

2027
CB
LEU
A
459
11.618
41.002
10.530
1.00
22.31

2028
CG
LEU
A
459
12.098
39.582
10.868
1.00
22.34

2029
CD1
LEU
A
459
11.955
39.318
12.368
1.00
23.76

2030
CD2
LEU
A
459
11.284
38.567
10.076
1.00
22.76

2031
C
LEU
A
459
13.872
41.998
10.930
1.00
22.18

2032
O
LEU
A
459
14.623
41.493
11.761
1.00
21.97

2033
N
LEU
A
460
14.301
42.438
9.753
1.00
21.66

2034
CA
LEU
A
460
15.710
42.337
9.397
1.00
21.60

2035
CB
LEU
A
460
15.892
42.619
7.902
1.00
20.70

2036
CG
LEU
A
460
14.974
41.760
7.022
1.00
19.18

2037
CD1
LEU
A
460
15.343
41.949
5.560
1.00
20.00

2038
CD2
LEU
A
460
15.098
40.285
7.418
1.00
16.85

2039
C
LEU
A
460
16.539
43.305
10.232
1.00
23.25

2040
O
LEU
A
460
17.679
43.015
10.606
1.00
21.71

2041
N
GLN
A
461
15.952
44.453
10.541
1.00
23.59

2042
CA
GLN
A
461
16.645
45.444
11.339
1.00
26.43

2043
CB
GLN
A
461
15.808
46.720
11.444
1.00
28.61

2044
CG
GLN
A
461
16.491
47.837
12.219
1.00
34.25

2045
CD
GLN
A
461
17.776
48.316
11.564
1.00
36.90

2046
OE1
GLN
A
461
18.513
49.110
12.145
1.00
40.50

2047
NE2
GLN
A
461
18.045
47.843
10.353
1.00
38.17

2048
C
GLN
A
461
16.950
44.899
12.734
1.00
25.75

2049
O
GLN
A
461
18.057
45.078
13.235
1.00
27.57

2050
N
GLU
A
462
15.989
44.224
13.361
1.00
25.39

2051
CA
GLU
A
462
16.241
43.696
14.699
1.00
26.81

2052
CB
GLU
A
462
14.930
43.290
15.401
1.00
28.93

2053
CG
GLU
A
462
14.134
42.155
14.784
1.00
30.21

2054
CD
GLU
A
462
12.838
41.880
15.553
1.00
32.16

2055
OE1
GLU
A
462
11.991
42.795
15.644
1.00
32.22

2056
OE2
GLU
A
462
12.665
40.755
16.071
1.00
30.73

2057
C
GLU
A
462
17.240
42.541
14.688
1.00
25.84

2058
O
GLU
A
462
17.970
42.332
15.659
1.00
25.91

2059
N
ILE
A
463
17.291
41.797
13.589
1.00
23.23

2060
CA
ILE
A
463
18.239
40.699
13.497
1.00
22.62

2061
CB
ILE
A
463
17.942
39.793
12.273
1.00
23.65

2062
CG2
ILE
A
463
19.115
38.833
12.020
1.00
21.96

2063
CG1
ILE
A
463
16.650
39.007
12.522
1.00
22.25

2064
CD1
ILE
A
463
16.196
38.160
11.338
1.00
24.20

2065
C
ILE
A
463
19.658
41.263
13.396
1.00
23.04

2066
O
ILE
A
463
20.568
40.782
14.062
1.00
20.73

2067
N
TYR
A
464
19.839
42.298
12.579
1.00
23.82

2068
CA
TYR
A
464
21.160
42.899
12.400
1.00
25.85

2069
CB
TYR
A
464
21.226
43.636
11.063
1.00
24.50

2070
CG
TYR
A
464
21.403
42.697
9.892
1.00
22.75

2071
CD1
TYR
A
464
22.563
41.933
9.758
1.00
23.07

2072
CE1
TYR
A
464
22.712
41.029
8.703
1.00
22.58

2073
CD2
TYR
A
464
20.397
42.538
8.943
1.00
23.44

2074
CE2
TYR
A
464
20.537
41.644
7.893
1.00
20.95

2075
CZ
TYR
A
464
21.692
40.894
7.779
1.00
22.05

2076
OH
TYR
A
464
21.819
40.001
6.744
1.00
21.31

2077
C
TYR
A
464
21.608
43.827
13.523
1.00
27.80

2078
O
TYR
A
464
22.803
44.064
13.685
1.00
28.04

2079
N
ARG
A
465
20.661
44.350
14.294
1.00
29.91

2080
CA
ARG
A
465
21.002
45.238
15.403
1.00
33.29

2081
CB
ARG
A
465
19.731
45.764
16.074
1.00
35.76

2082
CG
ARG
A
465
19.978
46.538
17.368
1.00
38.99

2083
CD
ARG
A
465
18.669
47.023
17.976
1.00
42.46

2084
NE
ARG
A
465
18.868
47.706
19.252
1.00
44.44

2085
CZ
ARG
A
465
17.897
48.297
19.943
1.00
46.85

2086
NH1
ARG
A
465
16.652
48.294
19.482
1.00
47.83

2087
NH2
ARG
A
465
18.167
48.890
21.097
1.00
47.38

2088
C
ARG
A
465
21.858
44.503
16.436
1.00
34.75

2089
O
ARG
A
465
21.406
43.540
17.055
1.00
34.47

2090
N
ASP
A
466
23.095
44.961
16.608
1.00
36.62

2091
CA
ASP
A
466
24.026
44.372
17.569
1.00
38.83

2092
CB
ASP
A
466
23.456
44.470
18.988
1.00
39.46

2093
CG
ASP
A
466
23.231
45.902
19.429
1.00
40.61

2094
OD1
ASP
A
466
24.151
46.729
19.242
1.00
40.51

2095
OD2
ASP
A
466
22.141
46.198
19.968
1.00
40.94

2096
C
ASP
A
466
24.407
42.921
17.288
1.00
39.96

2097
O
ASP
A
466
24.783
42.187
18.203
1.00
39.85

2098
N
MET
A
467
24.311
42.500
16.031
1.00
41.66

2099
CA
MET
A
467
24.674
41.132
15.678
1.00
43.69

2100
CB
MET
A
467
24.328
40.841
14.217
1.00
43.01

2101
CG
MET
A
467
24.631
39.416
13.797
1.00
43.53

2102
SD
MET
A
467
24.328
39.125
12.053
1.00
45.18

2103
CE
MET
A
467
22.544
38.865
12.066
1.00
44.23

2104
C
MET
A
467
26.175
40.966
15.889
1.00
45.56

2105
O
MET
A
467
26.619
40.175
16.722
1.00
46.26

2106
N
TYR
A
468
26.950
41.724
15.122
1.00
46.99

2107
CA
TYR
A
468
28.403
41.691
15.215
1.00
48.84

2108
CB
TYR
A
468
29.016
41.118
13.930
1.00
48.71

2109
CG
TYR
A
468
28.731
39.646
13.712
1.00
48.95

2110
CD1
TYR
A
468
27.913
39.218
12.665
1.00
49.23

2111
CE1
TYR
A
468
27.644
37.861
12.468
1.00
49.07

2112
CD2
TYR
A
468
29.273
38.680
14.560
1.00
49.57

2113
CE2
TYR
A
468
29.011
37.324
14.374
1.00
49.37

2114
CZ
TYR
A
468
28.197
36.921
13.328
1.00
49.98

2115
OH
TYR
A
468
27.940
35.580
13.147
1.00
49.98

2116
C
TYR
A
468
28.928
43.101
15.462
1.00
49.62

2117
O
TYR
A
468
29.141
43.829
14.472
1.00
50.21

2118
OT
TYR
A
468
29.091
43.471
16.646
1.00
50.66

2119
CB
GLU
B
685
18.548
43.302
21.979
1.00
63.65

2120
CG
GLU
B
685
18.317
43.165
23.475
1.00
63.87

2121
CD
GLU
B
685
18.479
41.737
23.956
1.00
64.23

2122
OE1
GLU
B
685
17.606
40.903
23.635
1.00
64.28

2123
OE2
GLU
B
685
19.478
41.445
24.647
1.00
64.53

2124
C
GLU
B
685
16.486
44.447
21.144
1.00
61.94

2125
O
GLU
B
685
15.986
44.713
20.050
1.00
62.27

2126
N
GLU
B
685
18.323
45.755
22.227
1.00
62.90

2127
CA
GLU
B
685
17.990
44.588
21.363
1.00
62.73

2128
N
ARG
B
686
15.773
44.020
22.185
1.00
60.58

2129
CA
ARG
B
686
14.324
43.847
22.118
1.00
59.13

2130
CB
ARG
B
686
13.677
45.103
21.527
1.00
60.07

2131
CG
ARG
B
686
12.155
45.100
21.495
1.00
61.27

2132
CD
ARG
B
686
11.558
45.589
22.807
1.00
62.16

2133
NE
ARG
B
686
10.176
46.030
22.634
1.00
63.43

2134
CZ
ARG
B
686
9.159
45.223
22.350
1.00
64.44

2135
NH1
ARG
B
686
9.361
43.920
22.210
1.00
64.89

2136
NH2
ARG
B
686
7.940
45.722
22.188
1.00
65.34

2137
C
ARG
B
686
13.919
42.623
21.291
1.00
57.39

2138
O
ARG
B
686
13.657
41.552
21.841
1.00
58.48

2139
N
HIS
B
687
13.874
42.792
19.972
1.00
54.71

2140
CA
HIS
B
687
13.488
41.724
19.049
1.00
51.16

2141
CB
HIS
B
687
14.325
40.462
19.290
1.00
51.72

2142
CG
HIS
B
687
15.785
40.639
19.009
1.00
51.47

2143
CD2
HIS
B
687
16.566
40.153
18.016
1.00
51.61

2144
ND1
HIS
B
687
16.608
41.410
19.801
1.00
52.04

2145
CE1
HIS
B
687
17.834
41.390
19.308
1.00
51.83

2146
NE2
HIS
B
687
17.835
40.635
18.225
1.00
51.34

2147
C
HIS
B
687
12.008
41.392
19.204
1.00
48.80

2148
O
HIS
B
687
11.637
40.237
19.403
1.00
48.44

2149
N
ALA
B
688
11.168
42.417
19.100
1.00
45.79

2150
CA
ALA
B
688
9.725
42.258
19.240
1.00
43.75

2151
CB
ALA
B
688
9.041
43.614
19.092
1.00
43.70

2152
C
ALA
B
688
9.115
41.263
18.255
1.00
41.94

2153
O
ALA
B
688
8.490
40.284
18.661
1.00
40.94

2154
N
ILE
B
689
9.295
41.517
16.963
1.00
40.75

2155
CA
ILE
B
689
8.740
40.649
15.931
1.00
39.42

2156
CB
ILE
B
689
9.107
41.161
14.523
1.00
39.12

2157
CG2
ILE
B
689
8.638
40.169
13.463
1.00
38.63

2158
OG1
ILE
B
689
8.460
42.530
14.296
1.00
38.90

2159
OD1
ILE
B
689
8.741
43.134
12.937
1.00
39.20

2160
C
ILE
B
689
9.189
39.200
16.077
1.00
38.83

2161
O
ILE
B
689
8.367
38.282
16.048
1.00
37.60

2162
N
LEU
B
690
10.491
38.998
16.238
1.00
38.40

2163
CA
LEU
B
690
11.033
37.656
16.393
1.00
38.63

2164
CB
LEU
B
690
12.548
37.730
16.597
1.00
39.36

2165
CG
LEU
B
690
13.382
36.561
16.069
1.00
40.30

2166
CD1
LEU
B
690
14.860
36.928
16.113
1.00
39.81

2167
CD2
LEU
B
690
13.108
35.314
16.889
1.00
41.50

2168
C
LEU
B
690
10.358
36.989
17.593
1.00
39.78

2169
O
LEU
B
690
9.895
35.850
17.505
1.00
38.83

2170
N
HIS
B
691
10.294
37.706
18.713
1.00
40.27

2171
CA
HIS
B
691
9.647
37.176
19.911
1.00
41.72

2172
CB
HIS
B
691
9.668
38.211
21.036
1.00
43.49

2173
CG
HIS
B
691
10.897
38.155
21.887
1.00
45.34

2174
CD2
HIS
B
691
11.909
39.040
22.053
1.00
46.24

2175
ND1
HIS
B
691
11.186
37.085
22.705
1.00
46.60

2176
CE1
HIS
B
691
12.322
37.313
23.339
1.00
46.83

2177
NE2
HIS
B
691
12.781
38.492
22.962
1.00
47.22

2178
C
HIS
B
691
8.205
36.799
19.596
1.00
41.36

2179
O
HIS
B
691
7.741
35.717
19.959
1.00
41.77

2180
N
ARG
B
692
7.502
37.698
18.915
1.00
40.51

2181
CA
ARG
B
692
6.112
37.459
18.543
1.00
40.58

2182
CB
ARG
B
692
5.588
38.617
17.692
1.00
41.97

2183
CG
ARG
B
692
4.108
38.532
17.339
1.00
44.31

2184
CD
ARG
B
692
3.755
39.573
16.287
1.00
46.39

2185
NE
ARG
B
692
4.450
39.308
15.029
1.00
48.87

2186
GZ
ARG
B
692
4.516
40.159
14.010
1.00
49.52

2187
NH1
ARG
B
692
3.929
41.346
14.093
1.00
50.67

2188
NH2
ARG
B
692
5.172
39.822
12.907
1.00
49.63

2189
C
ARG
B
692
5.998
36.152
17.760
1.00
39.77

2190
O
ARG
B
692
5.250
35.252
18.148
1.00
38.70

2191
N
LEU
B
693
6.746
36.052
16.663
1.00
38.99

2192
CA
LEU
B
693
6.730
34.854
15.825
1.00
39.44

2193
CB
LEU
B
693
7.812
34.932
14.741
1.00
38.36

2194
CG
LEU
B
693
7.643
35.944
13.604
1.00
38.71

2195
CD1
LEU
B
693
8.848
35.865
12.684
1.00
37.17

2196
CD2
LEU
B
693
6.365
35.657
12.828
1.00
37.74

2197
C
LEU
B
693
6.936
33.587
16.641
1.00
40.12

2198
O
LEU
B
693
6.290
32.569
16.399
1.00
40.20

2199
N
LEU
B
694
7.842
33.651
17.609
1.00
41.30

2200
CA
LEU
B
694
8.125
32.498
18.450
1.00
43.03

2201
CB
LEU
B
694
9.406
32.740
19.250
1.00
41.27

2202
CG
LEU
B
694
10.694
32.762
18.421
1.00
40.09

2203
CD1
LEU
B
694
11.853
33.242
19.269
1.00
39.04

2204
CD2
LEU
B
694
10.964
31.366
17.874
1.00
39.24

2205
C
LEU
B
694
6.974
32.178
19.399
1.00
45.64

2206
O
LEU
B
694
6.877
31.061
19.905
1.00
44.78

2207
N
GLN
B
695
6.099
33.153
19.628
1.00
49.29

2208
CA
GLN
B
695
4.967
32.964
20.532
1.00
53.51

2209
CB
GLN
B
695
4.350
34.316
20.912
1.00
53.94

2210
CG
GLN
B
695
5.336
35.354
21.441
1.00
54.96

2211
CD
GLN
B
695
6.069
34.916
22.699
1.00
55.61

2212
OE1
GLN
B
695
6.860
35.677
23.263
1.00
55.52

2213
NE2
GLN
B
695
5.814
33.690
23.144
1.00
55.62

2214
C
GLN
B
695
3.873
32.061
19.959
1.00
55.94

2215
O
GLN
B
695
3.035
31.553
20.702
1.00
55.76

2216
N
GLIJ
B
696
3.880
31.866
18.644
1.00
58.97

2217
CA
GLU
B
696
2.882
31.025
17.984
1.00
62.61

2218
CB
GLU
B
696
1.467
31.515
18.320
1.00
63.02

2219
CG
GLU
B
696
1.294
33.044
18.453
1.00
63.82

2220
CD
GLU
B
696
1.649
33.832
17.202
1.00
64.13

2221
OE1
GLU
B
696
1.115
33.519
16.115
1.00
64.51

2222
OE2
GLU
B
696
2.454
34.777
17.309
1.00
64.16

2223
C
GLU
B
696
3.055
31.054
16.473
1.00
64.98

2224
O
GLU
B
696
2.671
30.129
15.756
1.00
65.58

2225
N
GLY
B
697
3.643
32.150
16.021
1.00
67.35

2226
CA
GLY
B
697
3.875
32.400
14.618
1.00
70.03

2227
C
GLY
B
697
3.612
33.876
14.561
1.00
71.80

2228
O
GLY
B
697
3.004
34.366
13.584
1.00
71.76

2229
OT
GLY
B
697
4.003
34.560
15.534
1.00
71.76

2230
O
HOH
S
1
23.021
22.410
−2.190
1.00
19.60

2231
O
HOH
S
2
16.829
36.197
0.666
1.00
18.07

2232
O
HOH
S
3
22.165
35.434
11.145
1.00
15.63

2233
O
HOH
S
4
24.975
20.256
−2.262
1.00
20.14

2234
O
HOH
S
5
22.159
29.605
15.803
1.00
19.70

2235
O
HOH
S
6
24.989
31.512
−0.644
1.00
16.40

2236
O
HOH
S
7
10.834
33.694
−3.352
1.00
17.23

2237
O
HOH
S
8
22.460
38.715
−17.965
1.00
31.92

2238
O
HOH
S
9
17.528
31.039
1.273
1.00
14.10

2239
O
HOH
S
10
29.026
37.829
2.231
1.00
16.59

2240
O
HOH
S
11
16.137
33.624
0.850
1.00
17.71

2241
O
HOH
S
12
21.555
23.965
−0.430
1.00
13.97

2242
O
HOH
S
13
24.577
41.484
−5.877
1.00
19.10

2243
O
HOH
S
14
34.344
22.171
2.655
1.00
23.28

2244
O
HOH
S
15
23.968
19.698
−6.030
1.00
21.97

2245
O
HOH
5
16
12.341
31.084
−5.780
1.00
18.26

2246
O
HOH
S
17
17.291
24.202
0.490
1.00
21.48

2247
O
HOH
S
18
12.775
35.658
−4.277
1.00
15.87

2248
O
HOH
S
19
32.945
42.649
9.747
1.00
47.61

2249
O
HOH
S
20
6.636
45.304
0.256
1.00
32.40

2250
O
HOH
S
21
11.642
46.359
3.122
1.00
47.12

2251
O
HOH
S
22
15.366
32.455
−1.716
1.00
24.92

2252
O
HOH
S
23
15.186
49.092
−1.355
1.00
26.79

2253
O
HOH
S
24
17.321
27.755
27.447
1.00
23.87

2254
O
HOH
S
25
32.119
32.883
−0.957
1.00
24.24

2255
O
HOH
S
26
17.226
13.378
7.046
1.00
30.98

2256
O
HOH
S
27
17.607
52.477
−12.562
1.00
30.41

2257
O
HOH
S
28
11.582
28.462
0.833
1.00
27.74

2258
O
HOH
S
29
29.336
58.175
3.211
1.00
24.47

2259
O
110H
S
30
20.328
34.102
24.740
1.00
27.25

2260
O
HOH
S
31
11.297
30.724
−3.163
1.00
29.15

2261
O
HOH
S
32
14.539
17.647
−8.907
1.00
23.07

2262
O
HOH
S
33
12.598
30.559
30.560
1.00
24.86

2263
O
HOH
S
34
5.025
18.187
3.778
1.00
28.69

2264
O
HOH
S
35
14.927
26.075
0.820
1.00
31.48

2265
O
HOH
S
36
26.367
38.413
−9.182
1.00
23.21

2266
O
HOH
S
37
30.494
11.197
5.944
1.00
32.46

2267
O
HOH
S
38
11.293
49.824
6.074
1.00
48.93

2268
O
HOH
S
39
20.529
16.901
−4.931
1.00
32.28

2269
O
HOH
S
40
24.843
35.083
−15.519
1.00
21.88

2270
O
HOH
S
41
7.674
40.665
3.297
1.00
37.33

2271
O
HOH
S
42
27.523
46.282
−18.345
1.00
37.96

2272
O
HOH
S
43
22.709
13.774
−4.567
1.00
49.60

2273
O
HOH
S
44
7.423
32.242
11.910
1.00
23.05

2274
O
HOH
S
45
31.276
40.964
1.308
1.00
31.68

2275
O
HOH
S
46
33.265
32.328
3.517
1.00
19.13

2276
O
HOH
S
47
6.555
16.927
5.904
1.00
23.85

2277
O
HOH
S
48
17.606
50.658
7.865
1.00
28.11

2278
O
HOH
S
49
20.830
9.388
10.713
1.00
28.29

2279
O
HOH
S
50
13.364
37.050
29.629
1.00
23.94

2280
O
HOH
S
51
9.192
18.836
−1.960
1.00
33.23

2281
O
HOH
S
52
23.567
48.701
−14.763
1.00
55.81

2282
O
HOH
S
53
33.968
34.742
2.852
1.00
26.86

2283
O
HOH
S
54
29.820
10.990
8.338
1.00
28.51

2284
O
HOH
S
55
11.748
42.238
23.648
1.00
42.57

2285
O
HOH
S
56
14.767
33.631
−4.195
1.00
32.75

2286
O
HOH
S
57
12.500
34.343
29.890
1.00
22.65

2287
O
HOH
S
58
28.117
41.866
−15.415
1.00
31.74

2288
O
HOH
S
59
26.356
40.551
−7.512
1.00
22.73

2289
O
HOH
S
60
22.268
46.641
−15.890
1.00
50.83

2290
O
HOH
S
61
7.181
15.455
0.062
1.00
44.46

2291
O
HOH
S
62
3.620
30.584
−0.194
1.00
36.39

2292
O
HOH
S
63
6.128
27.849
3.787
1.00
52.56

2293
O
HOH
S
64
31.099
55.471
8.227
1.00
30.35

2294
O
HOH
S
65
18.603
58.163
−1.009
1.00
47.14

2295
O
HOH
S
66
8.356
23.629
26.974
1.00
32.72

2296
O
HOH
S
67
19.654
57.594
−3.383
1.00
43.61

2297
O
HOH
S
68
20.930
28.296
33.352
1.00
40.59

2298
O
HOH
S
69
21.652
36.732
27.720
1.00
35.00

2299
O
HOH
S
70
31.556
42.782
3.272
1.00
30.88

2300
O
HOH
S
71
13.327
50.293
2.487
1.00
38.75

2301
O
HOH
S
72
19.141
53.232
5.426
1.00
37.22

2302
O
HOH
S
73
10.869
22.357
19.472
1.00
19.26

2303
O
HOH
S
74
4.005
20.489
2.211
1.00
37.71

2304
O
HOH
S
75
32.792
10.675
9.182
1.00
22.60

2305
O
HOH
S
76
15.967
27.450
−1.311
1.00
30.63

2306
O
HOH
S
77
6.796
41.276
9.965
1.00
45.09

2307
O
HOH
S
78
6.261
30.440
7.929
1.00
33.02

2308
O
HOH
S
79
19.308
14.907
21.667
1.00
42.45

2309
O
HOH
S
80
2.565
29.418
1.814
1.00
40.89

2310
O
HOH
S
81
2.180
49.135
−16.647
1.00
53.37

2311
O
HOH
S
82
36.343
8.679
3.325
1.00
40.82

2312
O
HOH
S
83
22.711
19.517
29.686
1.00
47.69

2313
O
HOH
S
84
33.973
34.630
0.258
1.00
31.56

2314
O
HOH
S
85
31.745
38.264
1.536
1.00
22.56

2315
O
HOH
S
86
5.827
37.873
6.417
1.00
48.05

2316
O
HOH
S
87
19.499
17.423
−8.991
1.00
38.26

2317
O
HOH
S
88
40.418
35.587
7.944
1.00
35.76

2318
O
HOH
S
89
15.390
46.880
15.780
1.00
39.90

2319
O
HOH
S
90
6.878
29.542
−13.424
1.00
40.19

2320
O
HOH
S
91
8.647
28.612
20.656
1.00
29.73

2321
O
HOH
S
92
22.042
37.435
22.086
1.00
37.50

2322
O
HOH
S
93
27.585
30.929
23.977
1.00
32.74

2323
O
HOH
S
94
10.974
31.175
27.894
1.00
24.96

2324
O
HOH
S
95
26.202
25.474
−11.896
1.00
41.41

2325
O
HOH
S
96
6.726
33.443
−14.585
1.00
36.10

2326
O
HOH
S
97
15.550
8.924
10.717
1.00
33.88

2327
O
HOH
S
98
16.476
16.841
−2.591
1.00
26.55

2328
O
HOH
S
99
28.319
28.274
12.336
1.00
43.77

2329
O
HOH
S
100
27.769
3.457
13.155
1.00
48.23

2330
O
HOH
S
101
24.882
39.541
−19.201
1.00
53.25

2331
O
HOH
S
102
12.968
44.583
−8.525
1.00
25.37

2332
O
HOH
S
103
20.637
61.548
2.038
1.00
57.43

2333
O
HOH
S
104
18.394
21.172
−12.670
1.00
30.69

2334
O
HOH
S
105
21.685
40.720
28.499
1.00
31.23

2335
O
HOH
S
106
37.452
24.342
8.575
1.00
43.15

2336
O
HOH
S
107
28.072
12.030
−2.850
1.00
35.13

2337
O
HOH
S
108
13.643
6.793
9.813
1.00
59.43

2338
O
HOH
S
109
29.194
47.369
−11.513
1.00
33.93

2339
O
HOR
S
110
37.211
25.400
11.266
1.00
49.29

2340
O
HOH
S
111
32.452
24.117
12.117
1.00
37.91

2341
O
HOH
S
112
20.047
18.433
−15.782
1.00
52.69

2342
O
HOH
S
113
37.297
36.567
3.622
1.00
50.95

2343
O
HOH
S
114
26.638
37.932
27.578
1.00
60.19

2344
O
HOH
S
115
40.067
37.141
6.034
1.00
62.83

2345
O
HOH
S
116
16.702
28.787
32.709
1.00
45.22

2346
O
HOH
S
117
15.614
14.400
−2.970
1.00
32.52

2347
O
HOH
S
118
25.304
43.389
12.324
1.00
46.21

2348
O
HOH
S
119
35.986
27.446
−0.047
1.00
39.51

2349
O
HOH
S
120
33.667
38.724
−6.920
1.00
55.40

2350
O
HOH
S
121
2.653
22.799
6.024
1.00
32.62

2351
O
HOH
S
122
21.427
16.319
32.924
1.00
56.84

2352
O
HOH
S
123
2.535
25.653
7.482
1.00
49.14

2353
O
HOH
S
124
38.296
26.623
7.497
1.00
36.28

2354
O
HOH
S
125
24.325
56.054
−3.208
1.00
42.51

2355
O
HOH
S
126
31.374
39.772
−15.850
1.00
43.44

2356
O
HOH
S
127
14.293
49.969
9.738
1.00
46.86

2357
O
HOH
S
128
29.446
46.358
−15.130
1.00
56.58

2358
O
HOH
S
129
13.234
46.587
14.294
1.00
30.39

2359
O
HOH
S
130
28.696
21.460
14.541
1.00
43.43

2360
O
HOH
S
131
29.833
19.823
16.133
1.00
53.77

2361
O
HOH
S
132
28.668
40.610
0.027
1.00
27.60

2362
O
HOH
S
133
31.999
29.578
17.949
1.00
52.12

2363
O
HOH
S
134
32.331
41.291
−7.181
1.00
48.91

2364
O
HOH
S
135
18.143
37.552
22.925
1.00
31.27

2365
O
HOH
S
136
16.874
57.740
−7.181
1.00
36.07

2366
O
HOH
S
137
3.614
38.629
3.896
1.00
63.76

2367
O
HOH
S
138
18.541
13.341
−5.104
1.00
59.11

2368
O
HOH
S
139
6.118
51.002
−15.654
1.00
38.96

2369
O
HOH
S
140
14.730
25.982
29.459
1.00
32.23

2370
O
HOH
S
141
21.736
19.325
−8.319
1.00
36.70

2371
O
HOH
S
142
8.176
16.537
17.699
1.00
58.27

2372
O
HOH
S
143
11.696
32.975
0.495
1.00
36.22

2373
O
HOH
S
144
13.563
48.324
0.595
1.00
37.61

2374
O
HOH
S
145
12.379
12.447
17.047
1.00
62.89

2375
O
HOH
S
146
9.604
31.872
1.213
1.00
68.72

2376
O
HOH
S
147
28.144
19.163
18.746
1.00
42.30

2377
O
HOH
S
148
32.515
45.933
−7.466
1.00
37.61

2378
O
HOH
S
149
24.759
0.889
18.947
1.00
66.75

2379
O
HOH
S
150
39.683
22.653
2.230
1.00
35.42

2380
O
HOH
S
151
13.554
52.853
2.352
1.00
37.57

2381
O
HOH
S
152
8.318
48.977
2.507
1.00
73.06

2382
O
HOH
S
153
8.633
28.003
−12.609
1.00
33.91

2383
O
HOH
S
154
2.882
30.152
4.149
1.00
62.49

2384
O
HOH
S
155
31.535
7.386
4.692
1.00
35.95

2385
O
HOH
S
156
5.852
26.333
22.676
1.00
39.01

2386
O
HOH
S
157
7.617
46.335
−19.650
1.00
50.76

2387
O
HOH
S
158
23.004
9.857
−2.493
1.00
64.92

2388
O
HOH
S
159
6.680
37.243
8.927
1.00
35.74

2389
O
HOH
S
160
1.655
40.656
10.739
1.00
68.96

2390
O
HOH
S
161
37.861
28.017
11.079
1.00
29.28

2391
O
HOH
S
162
2.363
30.081
11.152
1.00
47.90

2392
O
HOH
S
163
22.816
6.883
24.251
1.00
50.27

2393
O
HOH
5
164
25.232
24.018
−9.509
1.00
56.25

2394
O
HOH
S
165
31.917
40.723
−4.749
1.00
43.99

2395
O
HOH
S
166
29.060
32.100
−14.160
1.00
48.37

2396
O
HOH
S
167
6.850
24.422
13.622
1.00
30.86

2397
O
HOH
S
168
31.128
26.378
−0.266
1.00
26.16

2398
O
HOH
S
169
26.393
4.775
16.316
1.00
46.62

2399
O
HOH
S
170
30.226
52.800
−0.982
1.00
62.86

2400
O
HOH
S
171
11.260
25.311
−15.954
1.00
30.67

2401
O
HOH
S
172
8.236
22.803
−8.257
1.00
36.47

2402
O
HOH
S
173
32.734
30.835
1.127
1.00
29.48

2403
O
HOH
S
174
12.162
13.528
−6.989
1.00
54.81

2404
O
HOH
S
175
10.004
18.589
−15.661
1.00
52.49

2405
O
HOH
S
176
2.597
15.841
3.847
1.00
36.47

2406
O
HOH
S
177
16.049
21.664
25.082
1.00
36.38

2407
O
HOH
S
178
9.566
53.021
5.395
1.00
51.65

2408
O
HOH
S
179
9.844
33.557
29.120
1.00
41.08

2409
O
HOH
S
180
28.907
9.505
−2.595
1.00
43.51

2410
O
HOH
S
181
29.014
14.102
−1.746
1.00
52.94

2411
O
HOH
S
182
8.615
16.558
11.985
1.00
34.51

2412
O
HOH
S
183
12.854
16.652
−1.111
1.00
38.29

2413
O
HOH
S
184
28.378
56.857
−0.308
1.00
70.56

2414
O
HOH
S
185
21.366
14.621
28.348
1.00
75.81

2415
O
HOH
S
186
29.539
7.952
13.215
1.00
47.28

2416
O
HOH
S
187
32.951
32.466
15.334
1.00
53.06

2417
O
HOH
S
188
6.055
23.083
15.885
1.00
44.59

2418
O
HOH
S
189
32.033
9.844
17.068
1.00
61.54

2419
O
HOH
S
190
31.234
15.535
16.608
1.00
47.53

2420
O
HOH
5
191
25.418
9.801
20.811
1.00
55.35

2421
O
HOH
S
192
17.915
17.399
−4.929
1.00
38.99

2422
O
HOH
S
193
20.092
56.578
−12.068
1.00
34.77

2423
O
HOH
S
194
5.198
29.909
5.015
1.00
54.91

2424
O
HOH
S
195
14.259
59.116
−6.790
1.00
57.78

2425
O
HOH
S
196
2.335
36.084
19.359
1.00
71.38

2426
O
HOH
S
197
25.907
29.027
30.690
1.00
45.68

2427
O
HOH
S
198
7.004
27.666
7.371
1.00
33.37

2428
O
HOH
S
199
29.917
10.266
3.633
1.00
28.69

2429
O
HOH
S
200
3.229
39.595
8.996
1.00
64.29

2430
O
HOH
S
201
11.658
26.014
31.457
1.00
30.92

2431
O
HOH
S
202
30.585
43.900
−10.316
1.00
35.47

2432
O
HOH
S
203
5.657
20.000
12.450
1.00
36.93

2433
O
HOH
S
204
9.001
8.083
12.525
1.00
44.27

2434
O
HOH
S
205
18.577
1.267
23.323
1.00
53.87

2435
O
HOH
S
206
14.129
50.521
−14.443
1.00
54.64

2436
O
HOH
S
207
18.959
15.493
28.375
1.00
71.59

2437
O
HOH
S
208
0.669
37.375
17.680
1.00
49.95

2438
O
HOH
S
209
26.872
55.578
−2.201
1.00
46.16

2439
O
HOH
S
210
6.168
22.883
11.718
1.00
31.87

2440
O
HOH
S
211
9.897
16.355
−1.729
1.00
36.68

2441
O
HOH
S
212
30.265
27.848
23.670
1.00
53.45

2442
O
HOH
S
213
30.762
47.558
−1.627
1.00
42.34

2443
O
HOH
S
214
32.189
35.014
15.024
1.00
44.29

2444
O
HOH
S
215
10.272
34.635
−0.779
1.00
25.15

2445
O
HOH
S
216
4.890
17.836
16.021
1.00
58.71

2446
O
HOH
S
217
5.733
41.605
7.246
1.00
41.48

2447
O
HOH
S
218
24.986
27.076
−7.629
1.00
61.37

2448
O
HOH
S
219
26.433
10.728
26.102
1.00
47.70

2449
O
HOH
S
220
9.403
26.411
28.194
1.00
51.51

2450
O
HOH
S
221
22.508
23.957
−9.377
1.00
43.79

2451
O
HOH
S
222
36.297
31.156
7.134
1.00
49.35

2452
O
HOH
S
223
16.073
56.555
4.729
1.00
47.51

2453
O
HOH
S
224
9.102
45.988
15.199
1.00
51.54

2454
O
HOH
S
225
22.868
15.999
−6.862
1.00
48.61

2455
O
HOH
S
226
4.554
37.721
10.138
1.00
63.61

2456
O
HOH
S
227
8.317
20.227
−8.684
1.00
40.62

2457
O
HOH
S
228
26.553
17.081
26.527
1.00
60.48

2458
O
HOH
S
229
18.435
52.120
−15.938
1.00
68.74

2459
O
HOH
S
230
15.731
11.256
6.138
1.00
40.27

2460
O
HOH
S
231
−2.470
33.671
15.319
1.00
56.63

2461
O
HOH
S
232
9.235
37.391
27.202
1.00
50.70

2462
O
HOH
S
233
22.857
5.454
−0.374
1.00
56.93

2463
O
HOH
S
234
1.412
28.065
19.093
1.00
54.97

2464
O
HOH
S
235
29.383
5.654
12.365
1.00
46.23

2465
O
HOH
S
236
21.394
2.024
21.053
1.00
54.78

2466
O
HOH
S
237
3.134
52.176
−19.288
1.00
61.95

2467
O
HOH
S
238
22.005
57.555
−0.605
1.00
48.17

2468
O
HOH
S
239
13.682
3.617
13.009
1.00
43.82

2469
O
HOH
S
240
19.176
16.596
19.466
1.00
31.39

2470
O
HOH
S
241
3.338
33.539
6.594
1.00
47.67

2471
O
HOH
S
242
10.760
2.995
19.481
1.00
70.14

2472
O
HOH
S
243
16.801
17.522
20.526
1.00
63.73

2473
O
HOH
S
244
2.600
44.637
16.700
1.00
56.53

2474
O
HOH
S
245
27.872
14.286
18.168
1.00
41.98

2475
O
HOH
S
246
31.396
45.519
−13.517
1.00
53.59

2476
O
HOH
S
247
31.244
35.576
−11.964
1.00
33.65

2477
O
HOH
S
248
21.693
4.459
26.360
1.00
52.63

2478
O
HOH
S
249
10.433
20.471
21.568
1.00
35.08

2479
O
HOH
S
250
17.785
18.041
18.016
1.00
49.80

2480
O
HOH
S
251
12.908
41.185
25.864
1.00
49.78

2481
O
HOH
S
252
11.825
38.262
27.686
1.00
41.47

2482
O
HOH
S
253
21.717
14.484
25.654
1.00
49.41

2483
O
HOH
S
254
3.264
19.434
−21.232
1.00
58.93

2484
O
HOH
S
255
32.144
44.531
−1.765
1.00
63.10

2485
O
HOH
S
256
30.528
19.733
26.321
1.00
56.72

2486
O
HOH
S
257
1.014
38.169
8.350
1.00
69.65

2487
O
HOH
S
258
15.650
56.451
−11.110
1.00
45.85

2488
O
HOH
S
259
9.637
49.206
−12.734
1.00
31.76

2489
O
HOH
S
260
26.271
33.962
11.972
1.00
28.74

2490
O
HOH
S
261
16.265
55.388
−6.013
1.00
48.50

2491
O
HOH
S
262
35.225
25.151
1.974
1.00
37.37

2492
O
HOH
S
263
34.131
31.093
10.695
1.00
35.88

2493
O
HOH
S
264
9.808
12.096
−10.102
1.00
42.96

2494
O
HOH
S
265
31.337
17.800
15.541
1.00
54.02

2495
O
HOH
S
266
6.034
17.605
1.265
1.00
32.48

2496
O
HOH
S
267
10.657
28.653
26.815
1.00
33.27

2497
O
HOH
S
268
33.123
28.220
0.778
1.00
32.26

2498
O
HOH
S
269
4.688
49.518
−17.401
1.00
56.01

2499
O
HOH
S
270
19.934
38.276
25.088
1.00
52.01

2500
O
HOH
S
271
17.067
16.746
−7.685
1.00
44.99

2501
O
HOH
S
272
8.184
32.997
31.099
1.00
38.13

2502
O
HOH
S
273
15.358
23.005
31.926
1.00
47.35

2503
O
HOH
S
274
37.594
33.163
10.831
1.00
50.51

2504
O
HOH
S
275
26.340
26.057
14.475
1.00
43.81

2505
O
HOH
S
276
9.314
11.770
3.305
1.00
52.95

2506
O
HOH
S
277
29.890
5.053
4.222
1.00
39.94

2507
O
HOH
S
278
21.596
63.668
5.719
1.00
47.51

2508
O
HOH
S
280
4.234
31.186
9.139
1.00
34.04

2509
O
HOH
S
281
20.211
52.099
−12.173
1.00
32.14

2510
O
HOH
S
282
31.764
46.901
−9.886
1.00
37.63

2511
O
HOH
S
283
29.356
16.377
18.834
1.00
47.88

2512
O
HOH
S
284
7.077
22.502
23.360
1.00
49.62

2513
O
HOH
S
285
10.457
17.845
24.918
1.00
45.38

2514
O
HOH
S
286
22.709
21.642
−7.858
1.00
44.54

2515
O
HOH
S
287
41.743
38.399
4.312
1.00
51.42

2516
O
HOH
S
288
28.342
29.192
29.846
1.00
35.37

2517
O
HOH
S
289
19.871
8.666
8.338
1.00
36.88

2518
O
HOH
S
290
30.239
47.828
14.437
1.00
52.48

2519
O
HOH
S
291
38.133
31.699
−0.085
1.00
48.80

2520
O
HOH
S
292
29.451
19.522
21.988
1.00
48.53

2521
O
HOH
S
293
28.207
17.784
23.529
1.00
49.19

2522
O
HOH
S
294
25.099
25.880
30.696
1.00
50.04

2523
O
HOH
S
295
20.984
24.305
−13.635
1.00
35.02

2524
O
HOH
S
296
27.314
9.229
14.571
1.00
37.16

2525
O
HOH
S
297
5.590
44.198
15.517
1.00
46.00

2526
O
HOH
S
298
1.452
15.832
16.496
1.00
48.72

2527
O
HOH
S
299
1.895
52.120
−9.294
1.00
36.65

2528
O
HOH
S
300
2.789
26.865
21.392
1.00
37.83

2529
O
HOH
S
301
10.822
21.853
1.469
1.00
38.42

2530
O
HOH
S
302
25.182
43.665
22.197
1.00
39.85

2531
O
HOH
S
303
10.013
44.307
3.131
1.00
61.53

2532
O
HOH
S
304
25.076
12.353
−5.192
1.00
49.90

2533
O
HOH
S
305
24.684
26.059
34.224
1.00
51.37

2534
O
HOH
S
306
17.636
17.778
−11.960
1.00
54.01

2535
O
HOH
S
307
21.679
9.218
−4.605
1.00
50.75

2536
O
HOH
S
308
12.832
30.478
−0.749
1.00
46.31

2537
O
HOH
S
309
−0.832
31.716
16.046
1.00
49.15

2538
O
HOH
S
310
11.345
25.092
29.161
1.00
54.91

2539
O
HOH
S
311
38.438
33.351
4.404
1.00
47.87

2540
O
HOH
S
312
29.760
48.475
−20.473
1.00
61.21

2541
O
HOH
S
313
19.889
22.967
34.487
1.00
53.69

2542
O
HOH
S
314
6.167
6.357
12.405
1.00
45.47

2543
O
HOH
S
315
24.800
24.028
−13.646
1.00
41.36

2544
O
HOH
S
316
34.408
33.833
13.704
1.00
48.67

2545
O
HOH
S
317
28.499
24.877
15.179
1.00
42.44

2546
O
HOH
S
318
18.760
10.026
−0.303
1.00
47.49

2547
O
HOH
S
319
27.889
33.343
15.965
1.00
46.60

2548
O
HOH
S
320
28.099
54.149
−9.913
1.00
47.31

2549
O
HOH
S
321
6.669
20.044
17.321
1.00
66.41

2550
O
HOH
S
322
9.183
51.425
−1.061
1.00
50.92

2551
O
HOH
S
323
26.136
49.957
−13.069
1.00
44.73

2552
O
HOH
S
324
6.462
14.964
10.693
1.00
50.61

2553
O
HOH
S
325
27.434
21.342
29.941
1.00
46.70

2554
O
HOH
S
326
−2.372
39.018
9.502
1.00
48.95

2555
O
HOH
S
327
39.676
34.723
11.054
1.00
54.77

2556
O
HOH
S
328
31.515
4.167
11.728
1.00
38.27

2557
O
HOH
S
329
30.273
43.414
12.468
1.00
56.22

2558
O
HOH
S
330
31.821
6.860
14.047
1.00
49.62

2559
O
HOH
S
331
34.176
36.382
−11.484
1.00
54.81

2560
O
HOH
S
332
16.341
29.905
−0.825
1.00
50.86

2561
O
HOH
S
333
16.034
14.050
−0.096
1.00
26.81

2562
O
HOH
S
334
35.569
39.304
6.909
1.00
58.70

2563
O
HOH
S
335
7.222
18.767
−13.380
1.00
48.09

2564
O
HOH
S
336
4.343
25.758
17.613
1.00
48.32

2565
O
HOH
S
337
23.980
49.898
20.317
1.00
45.46

2566
O
HOH
S
338
−1.308
39.173
20.570
1.00
47.06

2567
O
HOH
S
339
29.402
35.057
−23.568
1.00
51.53

2568
O
HOH
S
340
22.171
11.944
−8.266
1.00
58.38

2569
O
HOH
S
341
28.556
23.420
−8.393
1.00
38.50

2570
O
HOH
S
342
16.039
7.600
25.055
1.00
63.84

2571
O
HOH
S
343
2.335
34.042
2.843
1.00
52.94

2572
O
HOH
S
344
14.874
19.553
25.906
1.00
44.98

2573
O
HOH
S
345
33.947
47.332
−12.606
1.00
52.85

2574
O
HOH
S
346
27.488
24.767
30.391
1.00
48.33

2575
O
HOH
S
347
20.467
43.261
26.119
1.00
52.94

2576
O
HOH
S
348
28.263
37.781
30.518
1.00
62.99

2577
O
HOH
S
349
27.485
34.119
−15.359
1.00
50.71

2578
O
HOH
S
350
25.657
34.532
30.427
1.00
54.08

2579
O
HOH
S
351
29.768
1.154
1.312
1.00
59.34

2580
O
HOH
S
352
5.457
39.028
22.172
1.00
47.10

2581
O
HOH
S
353
5.067
16.762
20.070
1.00
60.26

2582
O
HOH
S
354
18.638
55.700
−4.851
1.00
,55.62

2583
O
HOH
S
355
32.686
59.039
10.830
1.00
39.90

2584
O
HOH
S
356
28.255
51.067
−11.879
1.00
52.57

2585
O
HOH
S
357
11.617
51.221
−1.789
1.00
63.06

2586
O
HOH
S
358
2.982
19.431
−24.499
1.00
45.57

2587
O
HOH
S
359
22.096
60.033
−1.451
1.00
61.45

2588
O
HOH
S
360
22.637
43.238
31.026
1.00
47.28

2589
O
HOH
S
361
30.447
38.954
29.873
1.00
57.25

2590
O
HOH
S
362
35.833
38.025
1.980
1.00
61.81

2591
O
HOH
S
363
6.113
31.893
−17.272
1.00
49.61

2592
O
HOH
S
364
6.724
15.601
−22.408
1.00
59.42

2593
O
HOH
S
365
12.111
1.178
18.316
1.00
48.35

2594
O
HOH
S
366
4.240
32.098
1.799
1.00
44.18

2595
O
HOH
S
367
29.724
35.065
27.753
1.00
55.76

2596
O
HOH
S
368
26.360
7.462
25.028
1.00
51.90

2597
O
HOH
S
369
9.107
46.874
3.890
1.00
56.70

2598
O
HOH
S
370
10.650
46.430
−20.344
1.00
37.21

2599
O
HOH
S
371
8.233
48.961
17.197
1.00
59.01

2600
O
HOH
S
372
20.322
15.007
−8.818
1.00
55.36

2601
O
HOH
S
373
19.260
−0.126
16.569
1.00
45.30

2602
O
HOH
S
374
7.343
49.778
−0.668
1.00
55.02

2603
O
HOH
S
375
2.507
47.867
0.719
1.00
48.12

2604
O
HOH
S
376
13.136
54.591
−2.145
1.00
53.44

2605
O
HOH
S
377
17.466
16.519
30.208
1.00
49.11

2606
O
HOH
S
378
20.118
10.769
23.252
1.00
55.34

2607
O
HOH
S
379
23.542
12.685
26.089
1.00
62.62

2608
O
HOH
S
380
20.375
47.120
12.159
1.00
51.92

2609
O
HOH
S
381
9.032
10.924
17.726
1.00
57.21

2610
O
HOH
S
382
15.077
15.226
30.470
1.00
56.74

2611
O
HOH
S
383
27.823
7.313
−8.539
1.00
49.75

2612
O
HOH
S
384
−1.210
31.371
18.699
1.00
53.14

2613
O
HOH
S
385
7.322
35.525
28.034
1.00
61.44

2614
O
HOH
S
386
14.217
16.674
−13.221
1.00
42.98

2615
O
HOH
S
387
20.0785
9.930
−2.925
1.00
54.66

2616
O
HOH
S
388
28.936
2.000
15.009
1.00
47.04

2617
O
HOH
S
389
14.166
28.692
31.577
1.00
59.65

2618
O
HOH
S
390
20.846
52.499
14.026
1.00
61.68

2619
O
HOH
S
391
13.294
5.368
25.444
1.00
52.09

2620
O
HOH
S
392
26.874
59.625
−2.846
1.00
46.54

2621
O
HOH
S
393
11.393
5.392
16.760
1.00
45.29

2622
O
HOH
S
394
30.608
57.650
11.108
1.00
63.95

2623
O
HOH
S
395
33.858
39.183
−13.250
1.00
54.28

2624
O
HOH
S
396
16.117
14.396
−7.011
1.00
46.14

2625
O
HOH
S
397
37.725
38.263
6.165
1.00
64.28

2626
O
HON
S
398
6.555
42.050
−19.474
1.00
48.56

2627
C1A
735
C
1
19.341
40.726
3.997
1.00
15.91

2628
O1C
735
C
1
18.234
40.214
4.328
1.00
17.26

2629
O1B
735
C
1
20.387
40.473
4.647
1.00
17.17

2630
C1D
735
C
1
19.458
41.690
2.760
1.00
14.73

2631
C1X
735
C
1
19.838
43.096
3.263
1.00
16.66

2632
C1Y
735
C
1
18.087
41.870
1.985
1.00
16.99

2633
O1E
735
C
1
20.617
41.213
1.907
1.00
15.62

2634
C1F
735
C
1
20.412
40.092
1.049
1.00
12.70

2635
G1G
735
C
1
20.433
40.315
−0.334
1.00
16.64

2636
G11
735
C
1
20.226
39.243
−1.204
1.00
15.86

2637
C1K
735
C
1
19.985
37.892
−0.696
1.00
15.12

2638
C11
735
C
1
19.969
37.669
0.700
1.00
15.25

2639
C1H
735
C
1
20.181
38.761
1.576
1.00
16.34

2640
C1L
735
C
1
19.744
36.701
−1.667
1.00
16.46

2641
N1M
735
C
1
19.050
37.255
−2.868
1.00
16.48

2642
C2A
735
C
1
17.700
37.386
−3.035
1.00
19.45

2643
O2A
735
C
1
16.905
37.016
−2.143
1.00
20.40

2644
S2C
735
C
1
15.441
38.082
−4.381
1.00
18.50

2645
C2B
735
C
1
17.156
37.942
−4.212
1.00
18.76

2646
C2D
735
C
1
17.793
38.466
−5.406
1.00
19.70

2647
C2G
735
C
1
19.306
38.558
−5.720
1.00
20.26

2648
N2E
735
C
1
16.928
38.919
−6.324
1.00
17.68

2649
C2F
735
C
1
15.614
38.789
−5.945
1.00
19.94

2650
C2H
735
C
1
14.528
39.186
−6.744
1.00
21.71

2651
C2J
735
C
1
13.173
39.004
−6.286
1.00
20.47

2652
C2L
735
C
1
12.084
39.400
−7.096
1.00
22.73

2653
C2M
735
C
1
12.305
−39.993
−8.391
1.00
20.47

2654
C2K
735
C
1
13.651
40.175
−8.842
1.00
23.90

2655
C2I
735
C
1
14.735
39.782
−8.042
1.00
22.13

2656
C2N
735
C
1
11.115
40.435
−9.308
1.00
25.97

2657
F2P
735
C
1
10.952
39.499
−10.296
1.00
31.88

2658
F2Q
735
C
1
9.934
40.532
−8.627
1.00
31.88

2659
F2O
735
C
1
11.362
41.644
−9.892
1.00
31.88

[0389]

6

TABLE 3

ATOMIC STRUCTURE COORDINATE DATA OBTAINED FROM X-RAY

DIFFRACTION FROM THE LIGAND BINDING DOMAIN OF PPARc USED IN

MOLECULAR REPLACEMENT

ATOM

PROTEIN

ATOM
TYPE
RESIDUE
#
#
X
Y
Z
OCC
B

1
CB
ASP
A
211
14.51
5.574
19.848
1.00
7846

2
CG
ASP
A
211
14.259
4.095
20.068
1.00
79.53

3
OD1
ASP
A
211
13.363
3.535
19.4
1.00
80.23

4
OD2
ASP
A
211
14.961
3.492
20.908
1.00
80.14

5
C
ASP
A
211
15.241
7.375
18.272
1.00
76.33

6
O
ASP
A
211
14.371
8.176
17.929
1.00
76.50

7
N
ASP
A
211
16.106
5.066
18.029
1.00
77.36

8
CA
ASP
A
211
14.923
5.889
18.409
1.00
77.08

9
N
LEU
A
212
16.49
7.738
18.549
1.00
74.80

10
CA
LEU
A
212
16.926
9.125
18.438
1.00
72.96

11
CB
LEU
A
212
18.142
9.393
19.328
1.00
73.58

12
CG
LEU
A
212
18.809
10.76
19.098
1.00
73.64

13
CD1
LEU
A
212
18.094
11.83
19.907
1.00
73.44

14
CD2
LEU
A
212
20.274
10.68
19.492
1.00
73.65

15
C
LEU
A
212
17.315
9.398
16.997
1.00
71.55

16
O
LEU
A
212
17.304
10.54
16.548
1.00
71.54

17
N
LYS
A
213
17.672
8.346
16.274
1.00
69.51

18
CA
LYS
A
213
18.069
8.512
14.89
1.00
67.63

19
CB
LYS
A
213
18.837
7.279
14.416
1.00
68.39

20
CG
LYS
A
213
19.477
7.423
13.047
1.00
68.94

21
CD
LYS
A
213
20.908
6.9
13.051
1.00
69.41

22
CE
LYS
A
213
21.036
5.602
13.837
1.00
69.58

23
NZ
LYS
A
213
22.361
4.97
13.652
1.00
70.30

24
C
LYS
A
213
16.845
8.769
14.018
1.00
65.91

25
O
LYS
A
213
16.97
9.16
12.856
1.00
66.04

26
N
SER
A
214
15.661
8.558
14.587
1.00
62.82

27
CA
SER
A
214
14.425
8.817
13.86
1.00
59.48

28
CB
SER
A
214
13.216
8.267
14.624
1.00
59.65

29
OG
SER
A
214
12.983
9
15.815
1.00
59.47

30
C
SER
A
214
14.326
10.34
13.76
1.00
56.82

31
O
SER
A
214
13.501
10.87
13.019
1.00
56.27

32
N
LEU
A
215
15.183
11.01
14.524
1.00
53.62

33
CA
LEU
A
215
15.244
12.47
14.553
1.00
50.75

34
CB
LEU
A
215
16.368
12.93
15.49
1.00
50.59

35
CG
LEU
A
215
16.736
14.42
15.548
1.00
49.94

36
CD1
LEU
A
215
15.58
15.23
16.111
1.00
49.18

37
CD2
LEU
A
215
17.975
14.6
16.414
1.00
49.63

38
C
LEU
A
215
15.496
13.02
13.155
1.00
48.97

39
O
LEU
A
215
15.029
14.1
12.809
1.00
49.11

40
N
ALA
A
216
16.238
12.26
12.355
1.00
46.47

41
CA
ALA
A
216
16.553
12.66
10.994
1.00
45.03

42
CB
ALA
A
216
17.423
11.61
10.322
1.00
44.87

43
C
ALA
A
216
15.288
12.9
10.169
1.00
44.53

44
O
ALA
A
216
15.076
14
9.662
1.00
43.47

45
N
LYS
A
217
14.446
11.88
10.041
1.00
43.76

46
CA
LYS
A
217
13.219
12.02
9.264
1.00
42.20

47
CB
LYS
A
217
12.458
10.69
9.203
1.00
44.47

48
CG
LYS
A
217
11.537
10.58
7.988
1.00
45.43

49
CD
LYS
A
217
10.703
9.314
7.994
1.00
46.92

50
CE
LYS
A
217
9.639
9.354
9.08
1.00
48.09

51
NZ
LYS
A
217
8.771
8.147
9.043
1.00
49.24

52
C
LYS
A
217
12.325
13.09
9.866
1.00
41.19

53
O
LYS
A
217
11.653
13.83
9.145
1.00
40.18

54
N
ARG
A
218
12.325
13.18
11.193
1.00
38.94

55
CA
ARG
A
218
11.534
14.18
11.901
1.00
37.26

56
CB
ARG
A
218
11.748
14.03
13.411
1.00
39.88

57
CG
ARG
A
218
11.396
15.26
14.24
1.00
43.03

58
CD
ARG
A
218
9.903
15.54
14.26
1.00
45.71

59
NE
ARG
A
218
9.619
16.9
14.734
1.00
46.98

60
CZ
ARG
A
218
8.399
17.41
14.851
1.00
47.56

61
NH1
ARG
A
218
7.335
16.68
14.531
1.00
48.63

62
NH2
ARG
A
218
8.242
18.65
15.28
1.00
47.03

63
C
ARG
A
218
11.948
15.58
11.444
1.00
34.87

64
O
ARG
A
218
11.109
16.39
11.052
1.00
33.63

65
N
ILE
A
219
13.247
15.86
11.5
1.00
31.60

66
CA
RE
A
219
13.762
17.16
11.084
1.00
28.45

67
CB
ILE
A
219
15.285
17.27
11.356
1.00
27.35

68
CG2
RE
A
219
15.874
18.46
10.625
1.00
26.86

69
CG1
RE
A
219
15.53
17.39
12.863
1.00
27.32

70
CD1
RE
A
219
16.997
17.3
13.258
1.00
26.22

71
C
RE
A
219
13.486
17.35
9.597
1.00
27.44

72
O
RE
A
219
13.153
18.45
9.153
1.00
26.71

73
N
TYR
A
220
13.619
16.28
8.834
1.00
25.68

74
CA
TYR
A
220
13.374
16.33
7.402
1.00
26.73

75
CB
TYR
A
220
13.786
15.01
6.748
1.00
25.17

76
CG
TYR
A
220
13.663
14.97
5.236
1.00
27.92

77
CD1
TYR
A
220
13.856
16.12
4.465
1.00
27.10

78
CE1
TYR
A
220
13.779
16.07
3.074
1.00
27.40

79
CD2
TYR
A
220
13.391
13.77
4.572
1.00
28.20

80
CE2
TYR
A
220
13.316
13.72
3.18
1.00
29.60

81
CZ
TYR
A
220
13.512
14.88
2.438
1.00
28.67

82
OH
TYR
A
220
13.453
14.83
1.062
1.00
30.22

83
C
TYR
A
220
11.895
16.64
7.155
1.00
26.35

84
O
TYR
A
220
11.554
17.41
6.263
1.00
22.94

85
N
GLU
A
221
11.013
16.04
7.948
1.00
27.41

86
CA
GLU
A
221
9.589
16.29
7.775
1.00
27.15

87
CB
GLU
A
221
8.76
15.39
8.694
1.00
29.37

88
CG
GLU
A
221
8.871
13.92
8.317
1.00
32.72

89
CD
GLU
A
221
7.949
13.01
9.119
1.00
34.56

90
OE1
GLU
A
221
8.047
13
10.363
1.00
36.22

91
OE2
GLU
A
221
7.127
12.31
8.498
1.00
36.44

92
C
GLU
A
221
9.301
17.77
8.056
1.00
25.89

93
O
GLU
A
221
8.54
18.4
7.329
1.00
25.26

94
N
ALA
A
222
9.929
18.3
9.099
1.00
23.75

95
CA
ALA
A
222
9.749
19.7
9.463
1.00
22.66

96
CB
ALA
A
222
10.526
20.02
10.733
1.00
24.94

97
C
ALA
A
222
10.225
20.6
8.325
1.00
21.68

98
O
ALA
A
222
9.625
21.64
8.041
1.00
20.08

99
N
TYR
A
223
11.311
20.2
7.678
1.00
20.59

100
CA
TYR
A
223
11.875
20.95
6.567
1.00
20.21

101
CB
TYR
A
223
13.226
20.34
6.205
1.00
21.59

102
CG
TYR
A
223
13.893
20.85
4.95
1.00
20.23

103
CD1
TYR
A
223
13.563
20.31
3.702
1.00
21.49

104
CE1
TYR
A
223
14.255
20.69
2.557
1.00
20.65

105
CD2
TYR
A
223
14.93
21.77
5.017
1.00
19.83

106
CE2
TYR
A
223
15.631
22.15
3.874
1.00
20.40

107
CZ
TYR
A
223
15.289
21.6
2.65
1.00
20.09

108
OH
TYR
A
223
16.005
21.93
1.52
1.00
22.28

109
C
TYR
A
223
10.919
20.96
5.371
1.00
20.36

110
O
TYR
A
223
10.657
22.01
4.78
1.00
18.08

111
N
LEU
A
224
10.374
19.8
5.03
1.00
19.65

112
CA
LEU
A
224
9.455
19.72
3.901
1.00
21.64

113
CB
LEU
A
224
9.163
18.25
3.565
1.00
22.15

114
CG
LEU
A
224
10.345
17.45
3.016
1.00
23.81

115
CD1
LEU
A
224
9.94
15.99
2.85
1.00
24.83

116
CD2
LEU
A
224
10.791
18.05
1.68
1.00
24.52

117
C
LEU
A
224
8.144
20.46
4.167
1.00
21.59

118
O
LEU
A
224
7.521
20.99
3.25
1.00
22.21

119
N
LYS
A
225
7.729
20.51
5.424
1.00
21.23

120
CA
LYS
A
225
6.482
21.17
5.776
1.00
24.07

121
CB
LYS
A
225
5.972
20.61
7.11
1.00
27.04

122
CG
LYS
A
225
4.766
21.32
7.725
1.00
32.48

123
CD
LYS
A
225
5.179
22.54
8.533
1.00
34.35

124
CE
LYS
A
225
3.985
23.17
9.244
1.00
36.46

125
NZ
LYS
A
225
4.381
24.35
10.071
1.00
35.63

126
C
LYS
A
225
6.571
22.69
5.862
1.00
23.63

127
O
LYS
A
225
5.582
23.39
5.616
1.00
22.64

128
N
ASN
A
226
7.757
23.21
6.177
1.00
21.43

129
CA
ASN
A
226
7.923
24.65
6.369
1.00
21.60

130
CB
ASN
A
226
8.631
24.88
7.704
1.00
21.30

131
CG
ASN
A
226
7.739
24.56
8.883
1.00
21.85

132
OD1
ASN
A
226
6.769
25.28
9.142
1.00
21.90

133
ND2
ASN
A
226
8.046
23.48
9.592
1.00
21.00

134
C
ASN
A
226
8.576
25.51
5.305
1.00
20.24

135
O
ASN
A
226
8.481
26.74
5.373
1.00
21.01

136
N
PHE
A
227
9.229
24.9
4.326
1.00
19.71

137
CA
PHE
A
227
9.883
25.69
3.279
1.00
20.43

138
CD
PHE
A
227
11.354
25.29
3.161
1.00
19.13

139
CG
PHE
A
227
12.162
25.6
4.392
1.00
18.17

140
CD1
PHE
A
227
12.348
26.92
4.801
1.00
16.25

141
CD2
PHE
A
227
12.736
24.58
5.136
1.00
16.60

142
CE1
PHE
A
227
13.094
27.21
5.935
1.00
16.71

143
CE2
PHE
A
227
13.488
24.86
6.275
1.00
17.69

144
CZ
PHE
A
227
13.668
26.18
6.678
1.00
18.05

145
C
PHE
A
227
9.185
25.5
1.941
1.00
21.87

146
O
PHE
A
227
9.147
24.41
1.401
1.00
23.21

147
N
ASN
A
228
8.644
26.59
1.407
1.00
22.66

148
CA
ASN
A
228
7.937
26.53
0.136
1.00
23.56

149
CB
ASN
A
228
7.251
27.87
−0.135
1.00
26.95

150
CG
ASN
A
228
6.072
28.12
0.801
1.00
29.92

151
OD1
ASN
A
228
5.14
27.31
0.867
1.00
33.43

152
ND2
ASN
A
228
6.108
29.23
1.528
1.00
32.80

153
C
ASN
A
228
8.842
26.14
−1.028
1.00
23.59

154
O
ASN
A
228
8.375
25.6
−2.029
1.00
22.24

155
N
MET
A
229
10.136
26.41
−0.891
1.00
22.41

156
CA
MET
A
229
11.09
26.05
−1.931
1.00
23.18

157
CB
MET
A
229
11.724
27.31
−2.537
1.00
23.66

158
CG
MET
A
229
12.717
27.05
−3.673
1.00
25.31

159
SD
MET
A
229
11.966
26.31
−5.134
1.00
26.48

160
CE
MET
A
229
10.916
27.66
−5.681
1.00
24.83

161
C
MET
A
229
12.175
25.18
−1.328
1.00
23.23

162
O
MET
A
229
12.629
25.42
−0.206
1.00
23.23

163
N
ASN
A
230
12.56
24.14
−2.067
1.00
21.71

164
CA
ASN
A
230
13.62
23.24
−1.638
1.00
22.22

165
CB
ASN
A
230
13.057
22.03
−0.889
1.00
23.15

166
CG
ASN
A
230
12.073
21.23
−1.712
1.00
24.30

167
OD1
ASN
A
230
12.321
20.93
−2.874
1.00
25.96

168
ND2
ASN
A
230
10.952
20.87
−1.1
1.00
26.83

169
C
ASN
A
230
14.37
22.82
−2.891
1.00
22.09

170
O
ASN
A
230
13.995
23.21
−3.997
1.00
20.57

171
N
LYS
A
231
15.42
22.03
−2.728
1.00
20.59

172
CA
LYS
A
231
16.235
21.61
−3.861
1.00
20.89

173
CB
LYS
A
231
17.466
20.85
−3.364
1.00
21.48

174
CG
LYS
A
231
18.656
20.95
−4.295
1.00
20.77

175
CD
LYS
A
231
19.92
20.5
−3.597
1.00
21.19

176
CE
LYS
A
231
21.125
20.63
−4.496
1.00
21.09

177
NZ
LYS
A
231
22.355
20.17
−3.814
1.00
19.55

178
C
LYS
A
231
15.503
20.79
−4.916
1.00
20.69

179
O
LYS
A
231
15.676
21.02
−6.11
1.00
19.10

180
N
VAL
A
232
14.694
19.82
−4.494
1.00
20.29

181
CA
VAL
A
232
13.956
19.02
−5.462
1.00
23.64

182
CB
VAL
A
232
13.006
18.01
−4.772
1.00
25.30

183
CG1
VAL
A
232
12.237
17.23
−5.824
1.00
28.94

184
CG2
VAL
A
232
13.796
17.07
−3.894
1.00
28.35

185
C
VAL
A
232
13.125
19.93
−6.371
1.00
22.27

186
O
VAL
A
232
13.222
19.84
−7.596
1.00
22.87

187
N
LYS
A
233
12.32
20.8
−5.762
1.00
22.90

188
CA
LYS
A
233
11.463
21.73
−6.505
1.00
22.56

189
CB
LYS
A
233
10.644
22.6
−5.544
1.00
25.17

190
CG
LYS
A
233
9.504
21.91
−4.817
1.00
25.33

191
CD
LYS
A
233
8.687
22.94
−4.048
1.00
27.14

192
CE
LYS
A
233
7.448
22.35
−3.407
1.00
27.11

193
NZ
LYS
A
233
6.64
23.42
−2.749
1.00
25.12

194
C
LYS
A
233
12.253
22.64
−7.438
1.00
23.61

195
O
LYS
A
233
11.887
22.83
−8.603
1.00
22.28

196
N
ALA
A
234
13.331
23.22
−6.917
1.00
22.21

197
CA
ALA
A
234
14.173
24.12
−7.696
1.00
21.88

198
CB
ALA
A
234
15.239
24.74
−6.796
1.00
19.12

199
C
ALA
A
234
14.839
23.43
−8.884
1.00
22.78

200
O
ALA
A
234
14.852
23.96
−9.989
1.00
23.11

201
N
ARG
A
235
15.395
22.24
−8.665
1.00
23.76

202
CA
ARG
A
235
16.064
21.52
−9.745
1.00
26.20

203
CB
ARG
A
235
16.735
20.25
−9.208
1.00
27.83

204
CG
ARG
A
235
18.065
20.54
−8.523
1.00
28.58

205
CD
ARG
A
235
19.004
21.27
−9.478
1.00
32.23

206
NE
ARG
A
235
20.002
22.08
−8.784
1.00
34.36

207
CZ
ARG
A
235
19.701
23.04
−7.919
1.00
37.04

208
NH1
ARG
A
235
18.431
23.31
−7.639
1.00
39.09

209
NH2
ARG
A
235
20.662
23.76
−7.352
1.00
35.24

210
C
ARG
A
235
15.153
21.19
−10.92
1.00
27.67

211
O
ARG
A
235
15.6
21.18
−12.07
1.00
29.64

212
N
VAL
A
236
13.881
20.92
−10.64
1.00
27.53

213
CA
VAL
A
236
12.921
20.63
−11.7
1.00
28.83

214
CB
VAL
A
236
11.55
20.23
−11.12
1.00
30.09

215
CG1
VAL
A
236
10.493
20.23
−12.22
1.00
31.75

216
CG2
VAL
A
236
11.641
18.85
−10.49
1.00
31.01

217
C
VAL
A
236
12.734
21.88
−12.55
1.00
28.74

218
O
VAL
A
236
12.763
21.83
−13.78
1.00
27.81

219
N
ILE
A
237
12.543
23.01
−11.87
1.00
26.31

220
CA
ILE
A
237
12.346
24.28
−12.54
1.00
26.14

221
CB
ILE
A
237
12.041
25.39
−11.51
1.00
24.59

222
CG2
ILE
A
237
12.015
26.76
−12.18
1.00
23.06

223
CG1
ILE
A
237
10.7
25.1
−10.83
1.00
23.57

224
CD1
ILE
A
237
10.402
26
−9.639
1.00
25.78

225
C
ILE
A
237
13.571
24.67
−13.37
1.00
28.37

226
O
ILE
A
237
13.441
25.23
−14.46
1.00
27.38

227
N
LEU
A
238
14.756
24.34
−12.86
1.00
28.44

228
CA
LEU
A
238
16.006
24.67
−13.54
1.00
31.74

229
CB
LEU
A
238
17.133
24.78
−12.52
1.00
30.50

230
CG
LEU
A
238
17.026
25.98
−11.57
1.00
30.22

231
CD1
LEU
A
238
18.016
25.83
−10.42
1.00
29.46

232
CD2
LEU
A
238
17.283
27.26
−12.35
1.00
29.52

233
C
LEU
A
238
16.415
23.68
−14.62
1.00
34.68

234
O
LEU
A
238
17.29
23.96
−15.44
1.00
35.11

235
N
SER
A
239
15.793
22.51
−14.62
1.00
37.91

236
CA
SER
A
239
16.1
21.48
−15.6
1.00
42.67

237
CB
SER
A
239
17.408
20.77
−15.26
1.00
42.74

238
OG
SER
A
239
18.474
21.25
−16.05
1.00
44.54

239
C
SER
A
239
14.991
20.46
−15.67
1.00
45.44

240
O
SER
A
239
14.579
19.89
−14.66
1.00
46.52

241
N
GLY
A
240
14.513
20.21
−16.88
1.00
48.97

242
CA
GLY
A
240
13.452
19.25
−17.04
1.00
52.46

243
C
GLY
A
240
12.655
19.58
−18.27
1.00
55.01

244
O
GLY
A
240
12.16
18.68
−18.93
1.00
55.62

245
N
LYS
A
241
12.554
20.88
−18.57
1.00
57.05

246
CA
LYS
A
241
11.817
21.41
−19.72
1.00
58.42

247
CB
LYS
A
241
12.707
21.39
−20.96
1.00
59.37

248
CG
LYS
A
241
13.824
22.43
−20.95
1.00
58.74

249
CD
LYS
A
241
14.872
22.09
−21.99
1.00
59.57

250
CE
LYS
A
241
15.865
23.22
−22.2
1.00
59.20

251
NZ
LYS
A
241
15.485
24.06
−23.36
1.00
60.11

252
C
LYS
A
241
10.514
20.68
−20.01
1.00
59.28

253
O
LYS
A
241
9.52
21.3
−20.37
1.00
59.75

254
N
ALA
A
242
10.544
19.36
−19.85
1.00
60.20

255
CA
ALA
A
242
9.408
18.47
−20.04
1.00
60.65

256
CB
ALA
A
242
9.225
17.59
−18.81
1.00
60.60

257
C
ALA
A
242
8.152
19.27
−20.3
1.00
61.11

258
O
ALA
A
242
7.718
19.43
−21.44
1.00
61.12

259
N
SER
A
243
7.581
19.79
−19.21
1.00
61.07

260
CA
SER
A
243
6.382
20.59
−19.3
1.00
61.06

261
CB
SER
A
243
5.726
20.72
−17.92
1.00
61.00

262
OG
SER
A
243
4.64
21.63
−17.95
1.00
59.89

263
G
SER
A
243
6.742
21.98
−19.84
1.00
61.10

264
O
SER
A
243
7.434
22.11
−20.85
1.00
61.74

265
N
ASN
A
244
6.279
23.01
−19.14
1.00
60.20

266
CA
ASN
A
244
6.53
24.38
−19.55
1.00
59.10

267
CB
ASN
A
244
5.91
24.6
−20.95
1.00
58.65

268
CG
ASN
A
244
5.63
26.05
−21.26
1.00
58.90

269
OD1
ASN
A
244
4.647
26.62
−20.78
1.00
59.73

270
ND2
ASN
A
244
6.488
26.66
−22.07
1.00
58.39

271
C
ASN
A
244
5.964
25.34
−18.5
1.00
58.52

272
O
ASN
A
244
5.616
24.91
−17.4
1.00
59.67

273
N
ASN
A
245
5.873
26.62
−18.85
1.00
56.14

274
CA
ASN
A
245
5.406
27.68
−17.94
1.00
51.26

275
CB
ASN
A
245
4.324
27.13
−17.01
1.00
52.89

276
CG
ASN
A
245
4.047
28.05
−15.84
1.00
52.48

277
OD1
ASN
A
245
3.453
29.12
−16
1.00
52.78

278
ND2
ASN
A
245
4.489
27.64
−14.66
1.00
52.90

279
C
ASN
A
245
6.685
28.03
−17.18
1.00
47.02

280
O
ASN
A
245
6.689
28.2
−15.96
1.00
47.14

281
N
PRO
A
246
7.789
28.19
−17.93
1.00
42.04

282
CD
PRO
A
246
7.619
28.47
−19.37
1.00
41.47

283
CA
PRO
A
246
9.161
28.51
−17.54
1.00
38.16

284
CB
PRO
A
246
9.88
28.58
−18.87
1.00
38.68

285
CG
PRO
A
246
8.86
29.26
−19.71
1.00
39.97

286
C
PRO
A
246
9.379
29.77
−16.74
1.00
34.87

287
O
PRO
A
246
8.668
30.76
−16.9
1.00
34.21

288
N
PRO
A
247
10.379
29.75
−15.85
1.00
32.12

289
CD
PRO
A
247
11.207
28.6
−15.43
1.00
32.31

290
CA
PRO
A
247
10.669
30.93
−15.04
1.00
29.30

291
CB
PRO
A
247
11.823
30.47
−14.14
1.00
29.79

292
CG
PRO
A
247
12.418
29.28
−14.88
1.00
32.45

293
C
PRO
A
247
11.053
32.07
−15.97
1.00
27.36

294
O
PRO
A
247
11.692
31.86
−17.01
1.00
25.06

295
N
PHE
A
248
10.639
33.28
−15.62
1.00
24.30

296
CA
PHE
A
248
10.943
34.45
−16.43
1.00
23.14

297
CB
PHE
A
248
10.004
35.6
−16.07
1.00
25.05

298
CG
PHE
A
248
10.098
36.76
−17.01
1.00
26.31

299
CD1
PHE
A
248
9.46
36.72
−18.25
1.00
27.99

300
CD2
PHE
A
248
10.865
37.87
−16.69
1.00
27.41

301
CE1
PHE
A
248
9.585
37.77
−19.15
1.00
28.47

302
CE2
PHE
A
248
10.999
38.93
−17.59
1.00
28.03

303
CZ
PHE
A
248
10.357
38.88
−18.82
1.00
29.16

304
C
PHE
A
248
12.371
34.87
−16.13
1.00
22.55

305
O
PHE
A
248
12.726
35.08
−14.98
1.00
19.83

306
N
VAL
A
249
13.188
35
−17.17
1.00
22.23

307
CA
VAL
A
249
14.578
35.38
−16.97
1.00
21.89

308
CB
VAL
A
249
15.49
34.73
−18.04
1.00
23.08

309
CG1
VAL
A
249
16.917
35.26
−17.91
1.00
22.71

310
CG2
VAL
A
249
15.484
33.21
−17.87
1.00
22.78

311
C
VAL
A
249
14.817
36.88
−16.96
1.00
22.84

312
O
VAL
A
249
14.41
37.61
−17.87
1.00
22.43

313
N
ILE
A
250
15.472
37.34
−15.89
1.00
20.77

314
CA
ILE
A
250
15.814
38.74
−15.73
1.00
20.91

315
CB
ILE
A
250
15.494
39.22
−14.3
1.00
20.98

316
CG2
ILE
A
250
15.899
40.69
−14.14
1.00
19.06

317
CG1
ILE
A
250
13.996
39.04
−14.02
1.00
19.24

318
CD1
ILE
A
250
13.602
39.29
−12.57
1.00
21.68

319
C
ILE
A
250
17.314
38.83
−16
1.00
21.63

320
O
ILE
A
250
18.134
38.4
−15.18
1.00
19.53

321
N
HIS
A
251
17.668
39.37
−17.17
1.00
20.99

322
CA
HIS
A
251
19.07
39.48
−17.56
1.00
22.26

323
CB
HIS
A
251
19.343
38.57
−18.76
1.00
24.28

324
CG
HIS
A
251
18.57
38.93
−19.99
1.00
24.97

325
CD2
HIS
A
251
17.449
38.4
−20.53
1.00
25.77

326
ND1
HIS
A
251
18.922
39.99
−20.8
1.00
27.65

327
CE1
HIS
A
251
18.049
40.09
−21.79
1.00
25.99

328
NE2
HIS
A
251
17.145
39.14
−21.65
1.00
26.18

329
C
HIS
A
251
19.535
40.9
−17.86
1.00
23.10

330
O
HIS
A
251
20.719
41.13
−18.11
1.00
21.51

331
N
ASP
A
252
18.601
41.85
−17.84
1.00
23.64

332
CA
ASP
A
252
18.912
43.26
−18.07
1.00
26.61

333
CB
ASP
A
252
19.179
43.55
−19.55
1.00
27.87

334
CG
ASP
A
252
17.985
43.26
−20.44
1.00
29.61

335
OD1
ASP
A
252
16.857
43.13
−19.92
1.00
28.47

336
OD2
ASP
A
252
18.181
43.18
−21.68
1.00
31.76

337
C
ASP
A
252
17.791
44.15
−17.55
1.00
27.23

338
O
ASP
A
252
16.797
43.67
−17.01
1.00
25.64

339
N
MET
A
253
17.951
45.46
−17.73
1.00
28.20

340
CA
MET
A
253
16.958
46.41
−17.25
1.00
28.88

341
CB
MET
A
253
17.459
47.83
−17.49
1.00
31.16

342
CC
MET
A
253
18.755
48.11
−16.76
1.00
33.46

343
SD
MET
A
253
18.548
48.1
−14.96
1.00
36.77

344
CE
MET
A
253
19.322
49.69
−14.59
1.00
37.18

345
C
MET
A
253
15.566
46.24
−17.84
1.00
28.34

346
O
MET
A
253
14.565
46.4
−17.14
1.00
27.10

347
N
GLU
A
254
15.493
45.89
−19.12
1.00
28.20

348
CA
GLU
A
254
14.199
45.71
−19.76
1.00
27.38

349
CB
GLU
A
254
14.368
45.54
−21.28
1.00
30.74

350
CC
GLU
A
254
13.066
45.25
−22
1.00
34.46

351
CD
GLU
A
254
13.222
45.23
−23.51
1.00
37.18

352
OE1
GLU
A
254
14.097
44.5
−24.02
1.00
38.99

353
OE2
GLU
A
254
12.46
45.95
−24.19
1.00
39.82

354
C
GLU
A
254
13.443
44.51
−19.19
1.00
26.77

355
O
GLU
A
254
12.267
44.62
−18.84
1.00
24.55

356
N
THR
A
255
14.116
43.37
−19.09
1.00
25.14

357
CA
THR
A
255
13.476
42.17
−18.55
1.00
22.92

358
CB
THR
A
255
14.335
40.91
−18.81
1.00
22.22

359
OG1
THR
A
255
15.677
41.13
−18.36
1.00
20.92

360
CG2
THR
A
255
14.349
40.58
−20.3
1.00
22.08

361
C
THR
A
255
13.167
42.3
−17.06
1.00
22.64

362
O
THR
A
255
12.277
41.62
−16.54
1.00
21.75

363
N
LEU
A
256
13.895
43.17
−16.36
1.00
21.77

364
CA
LEU
A
256
13.629
43.39
−14.94
1.00
20.25

365
CB
LEU
A
256
14.7
44.28
−14.29
1.00
20.20

366
CG
LEU
A
256
14.347
44.72
−12.86
1.00
18.26

367
CD1
LEU
A
256
14.292
43.5
−11.94
1.00
19.55

368
CD2
LEU
A
256
15.378
45.72
−12.34
1.00
17.68

369
C
LEU
A
256
12.282
44.09
−14.84
1.00
20.44

370
O
LEU
A
256
11.424
43.7
−14.06
1.00
19.24

371
N
GYS
A
257
12.092
45.13
−15.64
1.00
20.05

372
CA
CYS
A
257
10.828
45.85
−15.61
1.00
22.13

373
CB
GYS
A
257
10.893
47.09
−16.53
1.00
22.88

374
SG
GYS
A
257
12.084
48.36
−16
1.00
28.89

375
C
GYS
A
257
9.675
44.94
−16.02
1.00
22.46

376
O
CYS
A
257
8.588
45.02
−15.46
1.00
23.21

377
N
MET
A
258
9.915
44.06
−17
1.00
24.21

378
CA
MET
A
258
8.881
43.13
−17.47
1.00
25.70

379
CB
MET
A
258
9.383
42.33
−18.67
1.00
28.67

380
CG
MET
A
258
9.875
43.17
−19.85
1.00
34.04

381
SD
MET
A
258
10.485
42.19
−21.26
1.00
38.98

382
CE
MET
A
258
10.123
43.33
−22.62
1.00
38.27

383
C
MET
A
258
8.496
42.18
−16.34
1.00
25.87

384
O
MET
A
258
7.314
41.92
−16.1
1.00
25.43

385
N
ALA
A
259
9.503
41.64
−15.66
1.00
24.88

386
CA
ALA
A
259
9.262
40.72
−14.56
1.00
23.76

387
CB
ALA
A
259
10.586
40.19
−14.03
1.00
22.98

388
C
ALA
A
259
8.482
41.41
−13.44
1.00
22.99

389
O
ALA
A
259
7.546
40.83
−12.89
1.00
23.42

390
N
GLU
A
260
8.864
42.64
−13.12
1.00
22.90

391
CA
GLU
A
260
8.178
43.38
−12.07
1.00
23.30

392
CB
GLU
A
260
8.843
44.75
−11.85
1.00
23.04

393
CG
GLU
A
260
10.269
44.67
−11.31
1.00
23.77

394
CD
GLU
A
260
10.974
46.02
−11.26
1.00
25.32

395
OE1
GLU
A
260
10.929
46.75
−12.27
1.00
26.09

396
OE2
GLU
A
260
11.59
46.34
−10.23
1.00
24.65

397
C
GLU
A
260
6.717
43.57
−12.46
1.00
24.60

398
O
GLU
A
260
5.818
43.41
−11.64
1.00
23.99

399
N
LYS
A
261
6.489
43.91
−13.72
1.00
26.88

400
CA
LYS
A
261
5.138
44.13
−14.22
1.00
29.38

401
CB
LYS
A
261
5.18
44.42
−15.72
1.00
31.11

402
CG
LYS
A
261
3.818
44.72
−16.31
1.00
34.55

403
CD
LYS
A
261
3.758
46.12
−16.89
1.00
38.59

404
CE
LYS
A
261
4.149
47.18
−15.87
1.00
40.59

405
NZ
LYS
A
261
5.627
47.33
−15.75
1.00
42.89

406
C
LYS
A
261
4.233
42.92
−13.96
1.00
30.43

407
O
LYS
A
261
3.05
43.07
−13.65
1.00
30.61

408
N
THR
A
262
4.797
41.72
−14.08
1.00
31.64

409
CA
THR
A
262
4.031
40.5
−13.88
1.00
32.66

410
CB
THR
A
262
4.501
39.39
−14.85
1.00
34.32

411
OG1
THR
A
262
4.522
39.9
−16.19
1.00
37.49

412
CG2
THR
A
262
3.551
38.2
−14.79
1.00
34.76

413
C
THR
A
262
4.078
39.92
−12.47
1.00
32.57

414
O
THR
A
262
3.04
39.59
−11.89
1.00
33.27

415
N
LEU
A
263
5.279
39.8
−11.91
1.00
31.54

416
CA
LEU
A
263
5.453
39.21
−10.58
1.00
31.84

417
CB
LEU
A
263
6.819
38.53
−10.51
1.00
32.07

418
CG
LEU
A
263
6.945
37.14
−11.14
1.00
33.07

419
CD1
LEU
A
263
5.767
36.84
−12.06
1.00
32.88

420
CD2
LEU
A
263
8.261
37.06
41.88
1.00
32.53

421
C
LEU
A
263
5.275
40.13
−9.371
1.00
32.52

422
O
LEU
A
263
4.808
39.68
−8.319
1.00
31.50

423
N
VAL
A
264
5.662
41.39
−9.504
1.00
32.08

424
CA
VAL
A
264
5.532
42.35
−8.412
1.00
2.49

425
CB
VAL
A
264
6.897
42.61
−7.727
1.00
32.30

426
CG1
VAL
A
264
6.752
43.68
−6.667
1.00
33.97

427
CG2
VAL
A
264
7.403
41.32
−7.079
1.00
33.63

428
C
VAL
A
264
4.992
43.64
−9.009
1.00
33.56

429
O
VAI
A
264
5.659
44.68
−9.012
1.00
32.17

430
N
ALA
A
265
3.768
43.55
−9.518
1.00
34.97

431
CA
ALA
A
265
3.079
44.66
−10.17
1.00
35.76

432
CB
ALA
A
265
1.623
44.28
−10.4
1.00
37.47

433
C
ALA
A
265
3.148
46.04
−9.512
1.00
37.14

434
O
ALA
A
265
3.094
47.06
−10.21
1.00
35.98

435
N
LYS
A
266
3.271
46.1
−8.189
1.00
37.87

436
CA
LYS
A
266
3.313
47.39
−7.507
1.00
39.85

437
CB
LYS
A
266
3.159
47.21
−5.989
1.00
39.30

438
CG
LYS
A
266
3.099
48.54
−5.222
1.00
40.41

439
CD
LYS
A
266
3.065
48.35
−3.709
1.00
41.21

440
CE
LYS
A
266
1.695
47.91
−3.21
1.00
42.93

441
NZ
LYS
A
266
0.646
48.94
−3.476
1.00
44.25

442
C
LYS
A
266
4.565
48.24
−7.782
1.00
40.87

443
O
LYS
A
266
4.519
49.46
−7.702
1.00
41.16

444
N
LEU
A
267
5.675
47.58
−8.11
1.00
41.92

445
CA
LEU
A
267
6.922
48.3
−8.358
1.00
43.90

446
CB
LEU
A
267
8.114
47.38
−8.094
1.00
43.36

447
CG
LEU
A
267
8.078
46.63
−6.758
1.00
42.94

448
CD1
LEU
A
267
9.45
46.03
−6.48
1.00
42.92

449
CD2
LEU
A
267
7.673
47.57
−5.63
1.00
43.54

450
C
LEU
A
267
7.054
48.92
−9.748
1.00
45.44

451
O
LEU
A
267
8.128
49.41
−10.12
1.00
45.30

452
N
VAL
A
268
5.967
48.92
−10.51
1.00
47.08

453
CA
VAL
A
268
5.986
49.49
−11.85
1.00
49.10

454
CB
VAL
A
268
5.831
48.4
−12.93
1.00
49.12

455
CG1
VAL
A
268
7.032
47.47
−12.91
1.00
49.41

456
CG2
VAL
A
268
4.547
47.62
−12.69
1.00
49.20

457
C
VAL
A
268
4.876
50.52
−12.07
1.00
50.30

458
O
VAL
A
268
4.885
51.25
−13.06
1.00
50.13

459
N
ALA
A
269
3.929
50.57
−11.13
1.00
51.85

460
CA
ALA
A
269
2.799
51.49
−11.25
1.00
53.91

461
CB
ALA
A
269
1.491
50.71
−11.16
1.00
53.84

462
C
ALA
A
269
2.779
52.65
−10.26
1.00
55.04

463
O
ALA
A
269
1.788
53.37
−10.16
1.00
55.68

464
N
GLY
A
270
3.863
52.82
−9.508
1.00
55.70

465
CA
GLY
A
270
3.921
53.9
−8.54
1.00
57.57

466
C
GLY
A
270
5.338
54.41
−8.407
1.00
58.36

467
O
GLY
A
270
5.581
55.62
−8.394
1.00
58.74

468
N
ILE
A
271
6.272
53.47
−8.31
1.00
58.34

469
CA
ILE
A
271
7.695
53.76
−8.188
1.00
57.76

470
CB
ILE
A
271
8.424
52.63
−7.416
1.00
58.40

471
CG2
ILE
A
271
9.919
52.65
−7.72
1.00
58.51

472
CG1
ILE
A
271
8.159
52.76
−5.916
1.00
58.87

473
CD1
ILE
A
271
8.831
51.68
−5.081
1.00
59.43

474
C
ILE
A
271
8.307
53.86
−9.58
1.00
57.27

475
O
ILE
A
271
8.638
54.95
−10.06
1.00
57.93

476
N
GLN
A
272
8.435
52.7
−10.21
1.00
55.75

477
CA
GLN
A
272
9.007
52.52
−11.54
1.00
54.43

478
CB
GLN
A
272
7.969
52.82
−12.64
1.00
54.62

479
CG
GLN
A
272
7.554
54.26
−12.78
1.00
54.62

480
CD
GLN
A
272
6.052
54.43
−12.71
1.00
54.37

481
OE1
GLN
A
272
5.471
54.46
−11.63
1.00
54.65

482
NE2
GLN
A
272
5.411
54.52
−13.87
1.00
53.99

483
C
GLN
A
272
10.318
53.24
−11.84
1.00
53.23

484
O
GLN
A
272
11.049
52.83
−12.74
1.00
53.33

485
N
ASN
A
274
10.634
54.31
−11.11
1.00
51.79

486
CA
ASN
A
274
11.922
54.94
−11.37
1.00
50.16

487
CB
ASN
A
274
11.843
56.1
−12.34
1.00
52.29

488
CG
ASN
A
274
13.008
56.09
−13.33
1.00
54.63

489
OD1
ASN
A
274
13.481
57.13
−13.78
1.00
56.51

490
ND2
ASN
A
274
13.472
54.89
−13.67
1.00
55.84

491
C
ASN
A
274
12.762
55.35
−10.18
1.00
47.37

492
O
ASN
A
274
13.387
56.41
−10.18
1.00
47.22

493
N
LYS
A
275
12.732
54.52
−9.146
1.00
43.69

494
CA
LYS
A
275
13.627
54.71
−8.026
1.00
38.70

495
CB
LYS
A
275
13.13
53.98
−6.779
1.00
39.95

496
CG
LYS
A
275
11.997
54.69
−6.051
1.00
41.04

497
CD
LYS
A
275
11.744
54.06
−4.686
1.00
42.78

498
CE
LYS
A
275
10.677
54.82
−3.905
1.00
43.67

499
NZ
LYS
A
275
10.448
54.23
−2.551
1.00
44.37

500
C
LYS
A
275
14.632
53.86
−8.794
1.00
35.85

501
O
LYS
A
275
14.203
53.01
−9.578
1.00
32.72

502
N
GLU
A
276
15.934
54.07
−8.645
1.00
33.11

503
CA
GLU
A
276
16.802
53.24
−9.467
1.00
30.98

504
CB
GLU
A
276
18.279
53.64
−9.331
1.00
34.18

505
CG
GLU
A
276
18.874
53.68
−7.955
1.00
36.39

506
CD
GLU
A
276
20.194
54.43
−7.958
1.00
36.02

507
OE1
GLU
A
276
21.05
54.15
−8.823
1.00
36.54

508
OE2
GLU
A
276
20.376
55.31
−7.097
1.00
38.61

509
C
GLU
A
276
16.587
51.76
−9.234
1.00
29.49

510
O
GLU
A
276
16.175
51.32
−8.157
1.00
26.80

511
N
VAL
A
277
16.834
50.98
−10.28
1.00
26.80

512
CA
VAL
A
277
16.636
49.55
−10.23
1.00
27.28

513
CB
VAL
A
277
17.141
48.89
−11.52
1.00
26.70

514
CG1
VAL
A
277
16.422
49.49
−12.71
1.00
31.18

515
CG2
VAL
A
277
18.627
49.07
−11.64
1.00
31.22

516
C
VAL
A
277
17.268
48.84
−9.038
1.00
24.93

517
O
VAL
A
277
16.65
47.95
−8.457
1.00
23.64

518
N
GLU
A
278
18.487
49.23
−8.662
1.00
22.59

519
CA
GLU
A
278
19.126
48.56
−7.539
1.00
22.23

520
CB
GLU
A
278
20.549
49.1
−7.281
1.00
23.67

521
CG
GLU
A
278
20.912
50.44
−7.901
1.00
27.55

522
CD
GLU
A
278
21.043
50.38
−9.41
1.00
24.59

523
OE1
GLU
A
278
20.075
50.75
−10.08
1.00
26.10

524
OE2
GLU
A
278
22.104
49.96
−9.927
1.00
26.97

525
C
GLU
A
278
18.3
48.65
−6.26
1.00
22.57

526
O
GLU
A
278
18.329
47.74
−5.441
1.00
21.72

527
N
VAL
A
279
17.551
49.74
−6.094
1.00
21.59

528
CA
VAL
A
279
16.731
49.9
−4.895
1.00
21.26

529
CB
VAL
A
279
16.303
51.37
−4.721
1.00
23.06

530
CG1
VAL
A
279
15.292
51.5
−3.596
1.00
25.08

531
CG2
VAL
A
279
17.53
52.22
−4.415
1.00
25.52

532
G
VAL
A
279
15.5
49
−4.947
1.00
19.49

533
O
VAL
A
279
15.058
48.47
−3.918
1.00
18.78

534
N
ARG
A
280
14.956
48.81
−6.146
1.00
18.65

535
CA
ARG
A
280
13.796
47.94
−6.338
1.00
17.90

536
CB
ARG
A
280
13.243
48.1
−7.762
1.00
18.81

537
CG
ARG
A
280
12.211
49.2
−7.895
1.00
23.01

538
CD
ARG
A
280
12.321
49.93
−9.216
1.00
23.63

539
NE
ARG
A
280
12.387
49.04
−10.37
1.00
21.82

540
CZ
ARG
A
280
12.895
49.4
−11.55
1.00
23.69

541
NH1
ARG
A
280
13.376
50.63
−11.7
1.00
25.06

542
NH2
ARG
A
280
12.928
48.55
−12.56
1.00
24.09

543
C
ARG
A
280
14.217
46.49
−6.096
1.00
17.66

544
O
ARG
A
280
13.531
45.74
−5.405
1.00
16.97

545
N
ILE
A
281
15.356
46.11
−6.661
1.00
17.24

546
CA
ILE
A
281
15.877
44.76
−6.496
1.00
16.58

547
CB
ILE
A
281
17.152
44.55
−7.34
1.00
17.41

548
CG2
ILE
A
281
17.846
43.24
−6.943
1.00
17.49

549
CG1
ILE
A
281
16.779
44.56
−8.828
1.00
17.66

550
CD1
ILE
A
281
17.964
44.53
−9.781
1.00
19.17

551
C
ILE
A
281
16.192
44.5
−5.024
1.00
16.90

552
O
ILE
A
281
15.898
43.43
−4.497
1.00
16.85

553
N
PHE
A
282
16.776
45.5
−4.359
1.00
14.57

554
CA
PHE
A
282
17.111
45.36
−2.942
1.00
13.82

555
CB
PHE
A
282
17.886
46.59
−2.455
1.00
14.33

556
CG
PHE
A
282
18.48
46.42
−1.084
1.00
16.86

557
CD1
PHE
A
282
19.595
45.62
−0.894
1.00
17.16

558
CD2
PHE
A
282
17.927
47.07
0.014
1.00
16.21

559
CE1
PHE
A
282
20.157
45.46
0.364
1.00
18.94

560
CE2
PHE
A
282
18.481
46.92
1.28
1.00
19.15

561
CZ
PHE
A
282
19.601
46.11
1.456
1.00
20.18

562
C
PHE
A
282
15.848
45.21
−2.099
1.00
14.30

563
O
PHE
A
282
15.861
44.52
−1.085
1.00
15.47

564
N
HIS
A
283
14.766
45.87
−2.498
1.00
14.52

565
CA
HIS
A
283
13.517
45.76
−1.761
1.00
15.32

566
CB
HIS
A
283
12.454
46.7
−2.334
1.00
16.74

567
CG
HIS
A
283
11.139
46.6
−1.628
1.00
18.93

568
CD2
HIS
A
283
9.966
46.04
−1.999
1.00
21.47

569
ND1
HIS
A
283
10.95
47.07
−0.345
1.00
19.40

570
CE1
HIS
A
283
9.718
46.8
0.045
1.00
21.96

571
NE2
HIS
A
283
9.1
46.17
−0.94
1.00
23.33

572
C
HIS
A
283
13.03
44.31
−1.877
1.00
14.53

573
O
HIS
A
283
12.606
43.71
−0.9
1.00
15.83

574
N
CYS
A
284
13.089
43.77
−3.086
1.00
14.60

575
CA
CYS
A
284
12.668
42.39
−3.317
1.00
14.94

576
CB
CYS
A
284
12.713
42.06
−4.81
1.00
14.09

577
SG
CYS
A
284
11.464
42.95
−5.76
1.00
16.01

578
C
CYS
A
284
13.555
41.41
−2.539
1.00
14.97

579
O
CYS
A
284
13.09
40.37
−2.088
1.00
13.78

580
N
CYS
A
285
14.835
41.75
−2.385
1.00
15.23

581
CA
CYS
A
285
15.741
40.88
−1.626
1.00
13.47

582
CB
CYS
A
285
17.179
41.42
−1.666
1.00
15.89

583
SG
GYS
A
285
17.998
41.25
−3.256
1.00
15.55

584
C
CYS
A
285
15.266
40.84
−0.179
1.00
15.09

585
O
CYS
A
285
15.27
39.79
0.466
1.00
15.43

586
N
GLN
A
286
14.857
42
0.327
1.00
13.05

587
CA
GLN
A
286
14.375
42.1
1.7
1.00
14.74

588
CB
GLN
A
286
14.151
43.56
2.098
1.00
16.57

589
CG
GLN
A
286
15.42
44.38
2.198
1.00
18.11

590
CD
GLN
A
286
15.234
45.59
3.08
1.00
20.26

591
QEl
GLN
A
286
14.974
45.47
4.278
1.00
22.83

592
NE2
GLN
A
286
15.362
46.78
2.494
1.00
22.10

593
C
GLN
A
286
13.079
41.34
1.904
1.00
14.38

594
O
GLN
A
286
12.896
40.67
2.925
1.00
14.08

595
N
CYS
A
287
12.169
41.45
0.943
1.00
14.67

596
CA
CYS
A
287
10.905
40.74
1.063
1.00
15.04

597
CB
CYS
A
287
9.982
41.09
−0.104
1.00
16.30

598
SG
CYS
A
287
9.397
42.8
−0.06
1.00
22.25

599
C
CYS
A
287
11.187
39.24
1.091
1.00
14.70

600
O
CYS
A
287
10.587
38.5
1.864
1.00
14.34

601
N
THR
A
288
12.117
38.81
0.245
1.00
14.73

602
CA
THR
A
288
12.511
37.41
0.164
1.00
14.32

603
CB
THR
A
288
13.5
37.2
−1.003
1.00
15.37

604
OG1
THR
A
288
12.863
37.59
−2.233
1.00
13.87

605
CG2
THR
A
288
13.93
35.74
−1.1
1.00
14.11

606
C
THR
A
288
13.132
36.94
1.485
1.00
14.08

607
O
THR
A
288
12.771
35.89
2.023
1.00
13.41

608
N
SER
A
289
14.05
37.73
2.03
1.00
12.61

609
CA
SER
A
289
14.664
37.37
3.305
1.00
12.61

610
CB
SER
A
289
15.769
38.36
3.659
1.00
12.19

611
00
SER
A
289
16.916
38.11
2.875
1.00
11.40

612
C
SER
A
289
13.652
37.31
4.453
1.00
12.67

613
O
SER
A
289
13.72
36.42
5.289
1.00
12.90

614
N
VAL
A
290
12.71
38.25
4.493
1.00
13.57

615
CA
VAL
A
290
11.712
38.25
5.564
1.00
13.84

616
CB
VAL
A
290
10.78
39.48
5.455
1.00
15.55

617
CG1
VAL
A
290
9.541
39.31
6.333
1.00
17.55

618
CG2
VAL
A
290
11.549
40.72
5.887
1.00
16.53

619
C
VAL
A
290
10.905
36.96
5.536
1.00
15.35

620
O
VAL
A
290
10.64
36.35
6.578
1.00
14.98

621
N
GLU
A
291
10.536
36.52
4.338
1.00
16.73

622
CA
GLU
A
291
9.771
35.28
4.185
1.00
16.47

623
CB
OLU
A
291
9.329
35.11
2.729
1.00
19.03

624
CO
GLU
A
291
8.339
36.16
2.244
1.00
22.45

625
CD
GLU
A
291
6.917
35.91
2.726
1.00
27.72

626
OE1
GLU
A
291
6.712
35
3.567
1.00
28.03

627
OE2
GLU
A
291
6.003
36.62
2.261
1.00
27.23

628
C
GLU
A
291
10.604
34.08
4.61
1.00
15.29

629
O
GLU
A
291
10.107
33.19
5.286
1.00
14.93

630
N
THR
A
292
11.877
34.07
4.228
1.00
13.72

631
CA
THR
A
292
12.731
32.94
4.584
1.00
13.42

632
CB
THR
A
292
14.074
33.01
3.839
1.00
13.57

633
OG1
THR
A
292
13.825
33.11
2.428
1.00
13.65

634
CG2
THR
A
292
14.885
31.74
4.092
1.00
13.97

635
C
THR
A
292
12.966
32.88
6.091
1.00
13.92

636
O
THR
A
292
12.963
31.8
6.68
1.00
15.10

637
N
VAL
A
293
13.16
34.04
6.718
1.00
14.12

638
CA
VAL
A
293
13.357
34.07
8.172
1.00
14.58

639
CB
VAL
A
293
13.612
35.5
8.676
1.00
14.45

640
CG1
VAL
A
293
13.488
35.55
10.201
1.00
15.36

641
CG2
VAL
A
293
14.986
35.97
8.243
1.00
15.78

642
C
VAL
A
293
12.095
33.54
8.855
1.00
14.26

643
O
VAL
A
293
12.164
32.82
9.866
1.00
14.04

644
N
THR
A
294
10.941
33.9
8.304
1.00
15.03

645
CA
THR
A
294
9.667
33.45
8.859
1.00
16.55

646
CB
THR
A
294
8.491
34.13
8.119
1.00
17.70

647
OG1
THR
A
294
8.624
35.56
8.228
1.00
18.26

648
CG2
THR
A
294
7.154
33.71
8.721
1.00
18.59

649
C
THR
A
294
9.553
31.93
8.779
1.00
16.67

650
O
THR
A
294
9.122
31.28
9.731
1.00
15.85

651
N
GLU
A
295
9.953
31.35
7.65
1.00
16.45

652
CA
GLU
A
295
9.896
29.89
7.495
1.00
14.59

653
CB
GLU
A
295
10.204
29.48
6.047
1.00
17.05

654
CG
GLU
A
295
9.207
29.97
5.031
1.00
19.53

655
CD
GLU
A
295
9.556
29.51
3.623
1.00
21.27

656
OE1
GLU
A
295
10.759
29.44
3.297
1.00
24.29

657
OE2
GLU
A
295
8.628
29.24
2.845
1.00
26.60

658
C
GLU
A
295
10.892
29.18
8.419
1.00
15.53

659
O
GLU
A
295
10.591
28.13
8.986
1.00
14.95

660
N
LEU
A
296
12.084
29.76
8.554
1.00
14.15

661
CA
LEU
A
296
13.121
29.18
9.402
1.00
14.54

662
CB
LEU
A
296
14.421
29.98
9.243
1.00
13.35

663
CG
LEU
A
296
15.288
29.53
8.06
1.00
13.79

664
CD1
LEU
A
296
16.282
30.62
7.666
1.00
14.77

665
CD2
LEU
A
296
16.026
28.25
8.448
1.00
15.41

666
C
LEU
A
296
12.687
29.18
10.863
1.00
15.65

667
O
LEU
A
296
13.026
28.28
11.629
1.00
15.76

668
N
THR
A
297
11.942
30.21
11.241
1.00
16.74

669
CA
THR
A
297
11.467
30.33
12.613
1.00
17.31

670
CB
THR
A
297
10.823
31.72
12.827
1.00
17.24

671
OG1
THR
A
297
11.84
32.72
12.696
1.00
18.00

672
CG2
THR
A
297
10.184
31.83
14.216
1.00
18.26

673
C
THR
A
297
10.48
29.2
12.91
1.00
18.94

674
O
THR
A
297
10.518
28.61
13.99
1.00
18.36

675
N
GLU
A
298
9.61
28.9
11.947
1.00
18.64

676
CA
GLU
A
298
8.647
27.82
12.123
1.00
19.64

677
CB
GLU
A
298
7.585
27.87
11.023
1.00
20.78

678
CG
GLU
A
298
6.701
29.09
11.109
1.00
24.51

679
CD
GLU
A
298
5.986
29.17
12.439
1.00
27.16

680
OE1
GLU
A
298
5.16
28.28
12.715
1.00
28.65

681
OE2
GLU
A
298
6.256
30.12
13.208
1.00
29.29

682
C
GLU
A
298
9.375
26.48
12.099
1.00
19.12

683
O
GLU
A
298
9.006
25.55
12.817
1.00
19.43

684
N
PIlE
A
299
10.403
26.38
11.258
1.00
18.63

685
CA
PHE
A
299
11.205
25.15
11.174
1.00
18.56

686
CB
PHE
A
299
12.284
25.3
10.094
1.00
18.22

687
CG
PHE
A
299
13.287
24.17
10.078
1.00
16.52

688
OD1
PHE
A
299
12.909
22.89
9.711
1.00
15.73

689
CD2
PHE
A
299
14.622
24.41
10.407
1.00
16.62

690
CE1
PHE
A
299
13.842
21.85
9.667
1.00
16.62

691
CE2
PHE
A
299
15.56
23.39
10.367
1.00
16.63

692
CZ
PHE
A
299
15.168
22.1
9.992
1.00
16.10

693
C
PHE
A
299
11.887
24.9
12.52
1.00
19.02

694
O
PHE
A
299
11.855
23.78
13.041
1.00
19.20

695
N
ALA
A
300
12.519
25.93
13.068
1.00
19.85

696
CA
ALA
A
300
13.218
25.8
14.348
1.00
19.89

697
CB
ALA
A
300
13.855
27.13
14.739
1.00
20.05

698
C
ALA
A
300
12.267
25.34
15.448
1.00
21.19

699
O
ALA
A
300
12.627
24.5
16.284
1.00
19.62

700
N
LYS
A
301
11.059
25.89
15.447
1.00
21.75

701
CA
LYS
A
301
10.052
25.54
16.444
1.00
23.62

702
CB
LYS
A
301
8.8
26.4
16.253
1.00
22.82

703
CG
LYS
A
301
8.959
27.85
16.717
1.00
27.26

704
CD
LYS
A
301
7.814
28.74
16.225
1.00
30.13

705
CE
LYS
A
301
6.447
28.16
16.557
1.00
32.35

706
NZ
LYS
A
301
6.238
27.99
18.021
1.00
36.87

707
C
LYS
A
301
9.685
24.07
16.352
1.00
24.64

708
O
LYS
A
301
9.158
23.49
17.304
1.00
24.87

709
N
ALA
A
302
9.973
23.46
15.204
1.00
24.73

710
CA
ALA
A
302
9.674
22.05
14.987
1.00
24.93

711
CB
ALA
A
302
9.181
21.84
13.563
1.00
24.81

712
C
ALA
A
302
10.864
21.13
15.277
1.00
24.71

713
O
ALA
A
302
10.746
19.91
15.187
1.00
23.86

714
N
ILE
A
303
12.014
21.71
15.613
1.00
23.98

715
CA
ILE
A
303
13.179
20.89
15.932
1.00
22.06

716
CB
ILE
A
303
14.503
21.67
15.776
1.00
21.52

717
CG2
ILE
A
303
15.675
20.77
16.168
1.00
20.29

718
CG1
ILE
A
303
14.681
22.13
14.325
1.00
18.78

719
OD1
ILE
A
303
15.946
22.93
14.104
1.00
20.43

720
C
ILE
A
303
13.059
20.45
17.386
1.00
23.55

721
O
ILE
A
303
13.018
21.28
18.292
1.00
22.86

722
N
PRO
A
304
13
19.13
17.626
1.00
24.07

723
CD
PRO
A
304
13.119
18.03
16.644
1.00
23.94

724
CA
PRO
A
304
12.883
18.59
18.985
1.00
24.71

725
CB
PRO
A
304
13.275
17.13
18.804
1.00
24.70

726
CG
PRO
A
304
12.711
16.82
17.456
1.00
25.44

727
C
PRO
A
304
13.761
19.3
20.013
1.00
24.62

728
O
PRO
A
304
14.987
19.33
19.878
1.00
25.02

729
N
ALA
A
305
13.115
19.88
21.026
1.00
23.49

730
CA
ALA
A
305
13.788
20.58
22.124
1.00
23.80

731
CB
ALA
A
305
15.122
19.91
22.432
1.00
26.87

732
C
ALA
A
305
13.995
22.08
21.959
1.00
22.79

733
O
ALA
A
305
14.242
22.78
22.945
1.00
21.27

734
N
PHE
A
306
13.903
22.58
20.732
1.00
22.01

735
CA
PHE
A
306
14.101
24.01
20.515
1.00
22.24

736
CB
PHE
A
306
14.015
24.35
19.023
1.00
21.13

737
CG
PHE
A
306
14.301
25.8
18.714
1.00
20.73

738
CD1
PHE
A
306
13.293
26.76
18.775
1.00
21.28

739
CD2
PHE
A
306
15.591
26.21
18.393
1.00
20.25

740
CE1
PHE
A
306
13.568
28.1
18.519
1.00
20.90

741
CE2
PHE
A
306
15.875
27.55
18.136
1.00
19.14

742
CZ
PHE
A
306
14.864
28.5
18.199
1.00
19.75

743
C
PHE
A
306
13.088
24.85
21.285
1.00
22.26

744
O
PHE
A
306
13.448
25.84
21.936
1.00
22.51

745
N
ALA
A
307
11.821
24.46
21.215
1.00
23.86

746
CA
ALA
A
307
10.763
25.21
21.89
1.00
24.65

747
CB
ALA
A
307
9.399
24.7
21.441
1.00
25.58

748
C
ALA
A
307
10.868
25.16
23.413
1.00
25.96

749
O
ALA
A
307
10.238
25.96
24.102
1.00
26.50

750
N
ASN
A
308
11.667
24.23
23.932
1.00
26.32

751
CA
ASN
A
308
11.852
24.09
25.378
1.00
26.91

752
CB
ASN
A
308
12.291
22.67
25.717
1.00
27.32

753
CG
ASN
A
308
11.194
21.65
25.5
1.00
27.93

754
OD1
ASN
A
308
11.455
20.45
25.428
1.00
31.25

755
ND2
ASN
A
308
9.958
22.12
25.402
1.00
27.97

756
C
ASN
A
308
12.889
25.07
25.921
1.00
27.12

757
O
ASN
A
308
12.985
25.29
27.132
1.00
26.42

758
N
LEU
A
309
13.68
25.64
25.025
1.00
24.59

759
CA
LEU
A
309
14.702
26.6
25.428
1.00
23.00

760
CB
LEU
A
309
15.615
26.92
24.245
1.00
20.53

761
CG
LEU
A
309
16.484
25.8
23.676
1.00
20.80

762
CD1
LEU
A
309
17.175
26.3
22.414
1.00
20.69

763
CD2
LEU
A
309
17.512
25.37
24.714
1.00
21.60

764
C
LEU
A
309
14.041
27.87
25.91
1.00
21.59

765
O
LEU
A
309
12.89
28.13
25.582
1.00
20.49

766
N
ASP
A
310
14.767
28.65
26.701
1.00
23.45

767
CA
ASP
A
310
14.243
29.93
27.175
1.00
23.40

768
CB
ASP
A
310
15.263
30.64
28.062
1.00
22.34

769
CG
ASP
A
310
14.85
32.06
28.402
1.00
23.70

770
OD1
ASP
A
310
13.85
32.23
29.127
1.00
24.73

771
OD2
ASP
A
310
15.52
33
27.937
1.00
24.97

772
C
ASP
A
310
14.044
30.73
25.898
1.00
23.49

773
O
ASP
A
310
14.814
30.58
24.952
1.00
22.64

774
N
LEU
A
311
13.029
31.59
25.866
1.00
24.03

775
CA
LEU
A
311
12.762
32.38
24.669
1.00
24.61

776
CB
LEU
A
311
11.489
33.21
24.848
1.00
25.91

777
CG
LEU
A
311
11.312
34.15
26.038
1.00
29.90

778
CD1
LEU
A
311
12.37
35.25
26.043
1.00
31.19

779
CD2
LEU
A
311
9.925
34.77
25.94
1.00
32.22

780
C
LEU
A
311
13.916
33.28
24.225
1.00
23.78

781
O
LEU
A
311
14.075
33.54
23.035
1.00
22.46

782
N
ASN
A
312
14.713
33.77
25.17
1.00
22.87

783
CA
ASN
A
312
15.843
34.62
24.815
1.00
23.57

784
CB
ASN
A
312
16.501
35.19
26.072
1.00
24.41

785
CG
ASN
A
312
15.594
36.15
26.819
1.00
25.82

786
OD1
ASN
A
312
15.333
37.27
26.359
1.00
24.76

787
ND2
ASN
A
312
15.1
35.72
27.975
1.00
25.85

788
C
ASN
A
312
16.859
33.79
24.029
1.00
23.03

789
O
ASN
A
312
17.48
34.28
23.077
1.00
22.95

790
N
ASP
A
313
17.026
32.54
24.433
1.00
21.92

791
CA
ASP
A
313
17.959
31.66
23.751
1.00
21.37

792
CB
ASP
A
313
18.224
30.41
24.582
1.00
20.90

793
CG
ASP
A
313
19.281
30.63
25.649
1.00
20.90

794
OD1
ASP
A
313
19.785
31.77
25.768
1.00
22.16

795
OD2
ASP
A
313
19.609
29.67
26.364
1.00
22.62

796
C
ASP
A
313
17.411
31.28
22.383
1.00
20.42

797
O
ASP
A
313
18.176
31.07
21.442
1.00
21.27

798
N
GLN
A
314
16.088
31.2
22.268
1.00
19.98

799
CA
GLN
A
314
15.478
30.87
20.981
1.00
20.73

800
CB
GLN
A
314
13.971
30.64
21.124
1.00
20.41

801
CG
GLN
A
314
13.598
29.36
21.862
1.00
22.80

802
CD
GLN
A
314
12.1
29.12
21.906
1.00
24.47

803
OE1
GLN
A
314
11.425
29.14
20.876
1.00
26.99

804
NE2
GLN
A
314
11.571
28.89
23.104
1.00
23.97

805
C
GLN
A
314
15.74
32.04
20.03
1.00
19.47

806
O
GLN
A
314
16.099
31.84
18.869
1.00
19.20

807
N
VAL
A
315
15.561
33.25
20.541
1.00
19.92

808
CA
VAL
A
315
15.788
34.46
19.76
1.00
18.92

809
CB
VAL
A
315
15.414
35.72
20.583
1.00
19.64

810
CG1
VAL
A
315
15.861
36.98
19.867
1.00
20.62

811
CG2
VAL
A
315
13.91
35.75
20.794
1.00
19.50

812
C
VAL
A
315
17.246
34.55
19.321
1.00
18.13

813
O
VAL
A
315
17.538
34.84
18.157
1.00
17.71

814
N
THR
A
316
18.161
34.3
20.252
1.00
17.09

815
CA
THR
A
316
19.588
34.36
19.956
1.00
17.05

816
CB
THR
A
316
20.429
34.13
21.242
1.00
17.63

817
OG1
THR
A
316
20.162
35.19
22.17
1.00
16.06

818
CG2
THR
A
316
21.922
34.12
20.92
1.00
16.45

819
C
THR
A
316
20.007
33.34
18.889
1.00
16.61

820
O
THR
A
316
20.768
33.67
17.984
1.00
17.34

821
N
LEU
A
317
19.503
32.12
18.989
1.00
15.88

822
CA
LEU
A
317
19.864
31.09
18.018
1.00
16.20

823
CB
LEU
A
317
19.264
29.74
18.41
1.00
17.78

824
CG
LEU
A
317
19.886
29.11
19.656
1.00
16.63

825
CD1
LEU
A
317
19.277
27.73
19.916
1.00
17.89

826
CD2
LEU
A
317
21.393
29.01
19.46
1.00
17.96

827
C
LEU
A
317
19.417
31.48
16.616
1.00
16.44

828
O
LEU
A
317
20.147
31.27
15.643
1.00
17.08

829
N
LEU
A
318
18.221
32.05
16.507
1.00
16.59

830
CA
LEU
A
318
17.723
32.47
15.2
1.00
17.03

831
CB
LEU
A
318
16.209
32.72
15.255
1.00
16.97

832
CG
LEU
A
318
15.374
31.43
15.321
1.00
18.35

833
CD1
LEU
A
318
13.916
31.77
15.589
1.00
23.00

834
CD2
LEU
A
318
15.506
30.66
14.012
1.00
19.92

835
C
LEU
A
318
18.447
33.73
14.753
1.00
17.00

836
O
LEU
A
318
18.831
33.86
13.591
1.00
17.06

837
N
LYS
A
319
18.645
34.67
15.677
1.00
16.85

838
CA
LYS
A
319
19.332
35.91
15.335
1.00
17.88

839
CB
LYS
A
319
19.569
36.75
16.592
1.00
19.60

840
CG
LYS
A
319
20.244
38.09
16.315
1.00
21.39

841
CD
LYS
A
319
20.632
38.78
17.621
1.00
24.10

842
CE
LYS
A
319
21.26
40.14
17.374
1.00
24.44

843
NZ
LYS
A
319
20.287
41.09
16.751
1.00
26.22

844
C
LYS
A
319
20.671
35.66
14.634
1.00
18.39

845
O
LYS
A
319
20.961
36.28
13.609
1.00
19.24

846
N
TYR
A
320
21.475
34.75
15.177
1.00
16.44

847
CA
TYR
A
320
22.786
34.46
14.604
1.00
19.84

848
CB
TYR
A
320
23.781
34.13
15.721
1.00
23.67

849
CG
TYR
A
320
24.134
35.33
16.576
1.00
27.71

850
CD1
TYR
A
320
24.989
36.32
16.1
1.00
30.38

851
CE1
TYR
A
320
25.301
37.44
16.877
1.00
32.19

852
CD2
TYR
A
320
23.598
35.48
17.852
1.00
30.97

853
OE2
TYR
A
320
23.902
36.59
18.638
1.00
33.09

854
CZ
TYR
A
320
24.756
37.56
18.143
1.00
33.75

855
OH
TYR
A
320
25.075
38.65
18.916
1.00
36.85

856
C
TYR
A
320
22.8
33.33
13.577
1.00
17.92

857
O
TYR
A
320
23.708
33.26
12.747
1.00
20.86

858
N
GLY
A
321
21.795
32.47
13.612
1.00
16.75

859
CA
GLY
A
321
21.784
31.36
12.67
1.00
15.82

860
C
GLY
A
321
20.981
31.51
11.39
1.00
16.03

861
O
GLY
A
321
21.28
30.84
10.403
1.00
16.07

862
N
VAL
A
322
19.974
32.38
11.371
1.00
15.36

863
CA
VAL
A
322
19.162
32.5
10.167
1.00
16.30

864
CB
VAL
A
322
17.978
33.5
10.34
1.00
17.29

865
CG1
VAL
A
322
18.478
34.9
10.603
1.00
16.70

866
CG2
VAL
A
322
17.11
33.48
9.099
1.00
23.41

867
C
VAL
A
322
19.91
32.81
8.876
1.00
14.96

868
O
VAL
A
322
19.64
32.2
7.846
1.00
12.97

869
N
TYR
A
323
20.859
33.74
8.9
1.00
13.63

870
CA
TYR
A
323
21.544
34.05
7.651
1.00
14.50

871
CB
TYR
A
323
22.214
35.43
7.723
1.00
15.24

872
CG
TYR
A
323
21.209
36.52
7.416
1.00
15.95

873
CD1
TYR
A
323
20.791
36.76
6.108
1.00
16.47

874
CE1
TYR
A
323
19.768
37.66
5.83
1.00
17.10

875
CD2
TYR
A
323
20.586
37.23
8.446
1.00
15.91

876
CE2
TYR
A
323
19.569
38.14
8.182
1.00
15.61

877
CZ
TYR
A
323
19.161
38.35
6.875
1.00
16.58

878
OH
TYR
A
323
18.132
39.23
6.612
1.00
17.94

879
C
TYR
A
323
22.515
32.97
7.209
1.00
14.15

880
O
TYR
A
323
22.781
32.82
6.013
1.00
14.15

881
N
GLU
A
324
23.044
32.2
8.155
1.00
12.79

882
CA
GLU
A
324
23.94
31.11
7.77
1.00
13.63

883
CB
GLU
A
324
24.584
30.47
9.003
1.00
15.05

884
OG
GLU
A
324
25.608
31.38
9.689
1.00
15.42

885
CD
GLU
A
324
26.289
30.74
10.886
1.00
16.70

886
OE1
GLU
A
324
26.102
29.53
11.119
1.00
17.95

887
0E2
GLU
A
324
27.021
31.46
11.592
1.00
16.57

888
C
GLU
A
324
23.055
30.1
7.03
1.00
14.04

889
O
GLU
A
324
23.448
29.55
6.004
1.00
12.76

890
N
ALA
A
325
21.842
29.9
7.545
1.00
13.17

891
CA
ALA
A
325
20.904
28.96
6.931
1.00
13.03

892
CE
ALA
A
325
19.699
28.73
7.849
1.00
13.75

893
C
ALA
A
325
20.434
29.49
5.59
1.00
13.24

894
O
ALA
A
325
20.326
28.75
4.614
1.00
12.79

895
N
ILE
A
326
20.147
30.79
5.542
1.00
12.44

896
CA
ILE
A
326
19.692
31.4
4.306
1.00
11.19

897
CB
ILE
A
326
19.357
32.9
4.539
1.00
10.99

898
CG2
ILE
A
326
19.216
33.64
3.204
1.00
11.43

899
CG1
ILE
A
326
18.052
33
5.334
1.00
12.81

900
CD1
ILE
A
326
17.703
34.41
5.773
1.00
13.13

901
C
ILE
A
326
20.718
31.24
3.185
1.00
12.02

902
O
ILE
A
326
20.374
30.82
2.082
1.00
12.18

903
N
PHE
A
327
21.979
31.57
3.451
1.00
13.30

904
CA
PHE
A
327
22.982
31.43
2.395
1.00
13.60

905
CB
PHE
A
327
24.275
32.14
2.801
1.00
14.04

906
CG
PHE
A
327
24.093
33.61
3.059
1.00
13.96

907
CD1
PHE
A
327
23.199
34.36
2.295
1.00
16.84

908
CD2
PHE
A
327
24.819
34.25
4.054
1.00
15.29

909
CE1
PHE
A
327
23.028
35.73
2.519
1.00
17.71

910
CE2
PHE
A
327
24.657
35.62
4.284
1.00
18.04

911
CZ
PHE
A
327
23.755
36.35
3.511
1.00
15.92

912
C
PHE
A
327
23.232
29.96
2.027
1.00
13.74

913
O
PHE
A
327
23.537
29.64
0.878
1.00
13.80

914
N
ALA
A
328
23.104
29.05
2.994
1.00
13.03

915
CA
ALA
A
328
23.274
27.63
2.701
1.00
12.43

916
CB
ALA
A
328
23.255
26.8
4.003
1.00
11.53

917
C
ALA
A
328
22.127
27.18
1.783
1.00
13.70

918
O
ALA
A
328
22.342
26.48
0.788
1.00
13.68

919
N
MET
A
329
20.905
27.61
2.105
1.00
12.83

920
CA
MET
A
329
19.753
27.23
1.293
1.00
11.87

921
CB
MET
A
329
18.444
27.43
2.073
1.00
14.42

922
CG
MET
A
329
18.372
26.58
3.35
1.00
16.28

923
SD
MET
A
329
16.756
26.61
4.147
1.00
18.54

924
CE
MET
A
329
16.622
28.35
4.55
1.00
20.41

925
C
MET
A
329
19.691
27.94
−0.056
1.00
13.87

926
O
MET
A
329
19.027
27.47
−0.973
1.00
12.13

927
N
LEU
A
330
20.378
29.08
−0.193
1.00
13.97

928
CA
LEU
A
330
20.373
29.77
−1.484
1.00
15.41

929
CB
LEU
A
330
21.225
31.05
−1.43
1.00
15.37

930
CG
LEU
A
330
20.549
32.29
−0.84
1.00
18.20

931
CD1
LEU
A
330
21.486
33.49
−0.972
1.00
19.32

932
CD2
LEU
A
330
19.227
32.56
−1.56
1.00
18.93

933
C
LEU
A
330
20.934
28.85
−2.557
1.00
13.60

934
O
LEU
A
330
20.493
28.86
−3.707
1.00
15.79

935
N
SER
A
331
21.921
28.05
−2.167
1.00
12.99

936
CA
SER
A
331
22.574
27.11
−3.073
1.00
14.61

937
CB
SER
A
331
23.539
26.23
−2.277
1.00
14.55

938
OG
SER
A
331
24.355
27.04
−1.445
1.00
15.05

939
C
SER
A
331
21.553
26.24
−3.8
1.00
15.16

940
O
SER
A
331
21.739
25.88
−4.966
1.00
16.58

941
N
SER
A
332
20.474
25.89
−3.105
1.00
14.05

942
CA
SER
A
332
19.441
25.04
−3.685
1.00
14.37

943
CB
SER
A
332
18.391
24.7
−2.63
1.00
16.17

944
OG
SER
A
332
18.992
24.05
−1.527
1.00
14.97

945
C
SER
A
332
18.744
25.67
−4.889
1.00
15.39

946
O
SER
A
332
18.262
24.95
−5.768
1.00
15.48

947
N
VAL
A
333
18.677
26.99
−4.925
1.00
16.08

948
CA
VAL
A
333
18.002
27.67
−6.023
1.00
16.93

949
CB
VAL
A
333
16.985
28.72
−5.502
1.00
18.06

950
CG1
VAL
A
333
15.878
28.03
−4.717
1.00
20.27

951
CG2
VAL
A
333
17.692
29.76
−4.636
1.00
19.05

952
C
VAL
A
333
18.968
28.36
−6.971
1.00
16.26

953
O
VAL
A
333
18.55
29.14
−7.819
1.00
17.98

954
N
MET
A
334
20.253
28.03
−6.85
1.00
16.16

955
CA
MET
A
334
21.277
28.65
−7.697
1.00
17.20

956
CB
MET
A
334
22.358
29.32
−6.844
1.00
16.55

957
CG
MET
A
334
21.95
30.52
−6.005
1.00
16.51

958
SD
MET
A
334
23.363
31.08
−4.983
1.00
17.83

959
CE
MET
A
334
22.981
32.82
−4.792
1.00
19.15

960
C
MET
A
334
22.02
27.67
−8.596
1.00
19.13

961
O
MET
A
334
22.099
26.47
−8.312
1.00
20.24

962
N
ASN
A
335
22.555
28.19
−9.694
1.00
19.31

963
CA
ASN
A
335
23.426
27.42
−10.57
1.00
20.10

964
CB
ASN
A
335
22.721
26.85
−11.81
1.00
21.23

965
CG
ASN
A
335
22.146
27.9
−12.73
1.00
20.10

966
OD1
ASN
A
335
22.65
29.02
−12.83
1.00
21.27

967
ND2
ASN
A
335
21.089
27.53
−13.45
1.00
23.09

968
C
ASN
A
335
24.501
28.46
−10.9
1.00
21.45

969
O
ASN
A
335
24.433
29.58
−10.42
1.00
19.65

970
N
LYS
A
336
25.49
28.1
−11.71
1.00
21.83

971
CA
LYS
A
336
26.563
29.04
−12.01
1.00
23.64

972
CB
LYS
A
336
27.652
28.36
−12.84
1.00
26.31

973
CG
LYS
A
336
27.281
28.12
−14.3
1.00
30.33

974
CD
LYS
A
336
28.501
27.65
−15.09
1.00
34.09

975
CE
LYS
A
336
28.258
27.65
−16.6
1.00
36.35

976
NZ
LYS
A
336
27.211
26.68
−17.02
1.00
39.18

977
G
LYS
A
336
26.161
30.34
−12.7
1.00
22.90

978
O
LYS
A
336
26.927
31.31
−12.67
1.00
22.33

979
N
ASP
A
337
24.968
30.39
−13.28
1.00
21.50

980
CA
ASP
A
337
24.547
31.58
−14.01
1.00
21.46

981
CB
ASP
A
337
24.108
31.19
−15.42
1.00
22.79

982
CG
ASP
A
337
25.223
30.54
−16.21
1.00
24.81

983
OD1
ASP
A
337
26.326
31.12
−16.28
1.00
28.16

984
OD2
ASP
A
337
24.997
29.45
−16.76
1.00
26.38

985
C
ASP
A
337
23.466
32.47
−13.4
1.00
19.81

986
O
ASP
A
337
23.137
33.51
−13.96
1.00
18.99

987
N
GLY
A
338
22.91
32.06
−12.26
1.00
18.40

988
CA
GLY
A
338
21.877
32.88
−11.65
1.00
17.35

989
C
GLY
A
338
21.094
32.14
−10.58
1.00
16.28

990
O
GLY
A
338
21.473
31.04
−10.18
1.00
15.47

991
N
MET
A
339
20.001
32.74
−10.13
1.00
17.05

992
CA
MET
A
339
19.183
32.11
−9.093
1.00
17.55

993
CB
MET
A
339
19.562
32.65
−7.705
1.00
19.90

994
CG
MET
A
339
19.227
34.1
−7.44
1.00
22.04

995
SD
MET
A
339
19.422
34.52
−5.667
1.00
24.36

996
CE
MET
A
339
17.862
34.13
−5.025
1.00
23.38

997
C
MET
A
339
17.69
32.3
−9.315
1.00
17.11

998
O
MET
A
339
17.25
33.26
−9.943
1.00
17.45

999
N
LEU
A
340
16.91
31.35
−8.803
1.00
16.64

1000
CA
LEU
A
340
15.462
31.41
−8.914
1.00
16.30

1001
CB
LEU
A
340
14.848
30.05
−8.591
1.00
17.42

1002
CG
LEU
A
340
15.023
28.95
−9.62
1.00
19.04

1003
CD1
LEU
A
340
14.407
27.65
−9.08
1.00
18.84

1004
CD2
LEU
A
340
14.353
29.37
−10.92
1.00
17.82

1005
C
LEU
A
340
14.93
32.41
−7.908
1.00
16.49

1006
O
LEU
A
340
15.41
32.46
−6.776
1.00
17.61

1007
N
VAL
A
341
13.937
33.2
−8.314
1.00
14.86

1008
CA
VAL
A
341
13.333
34.17
−7.42
1.00
15.11

1009
CB
VAL
A
341
13.879
35.61
−7.673
1.00
14.89

1010
CG1
VAL
A
341
15.402
35.61
−7.55
1.00
17.85

1011
CG2
VAL
A
341
13.446
36.11
−9.045
1.00
16.47

1012
C
VAL
A
341
11.821
34.19
−7.593
1.00
14.36

1013
O
VAL
A
341
11.279
33.55
−8.499
1.00
15.87

1014
N
ALA
A
342
11.15
34.93
−6.717
1.00
13.97

1015
CA
ALA
A
342
9.701
35.07
−6.753
1.00
14.91

1016
CB
ALA
A
342
9.29
35.9
−7.966
1.00
15.58

1017
C
ALA
A
342
8.981
33.72
−6.768
1.00
14.63

1018
O
ALA
A
342
8.176
33.44
−7.664
1.00
14.60

1019
N
TYR
A
343
9.281
32.9
−5.769
1.00
14.26

1020
CA
TYR
A
343
8.655
31.59
−5.627
1.00
15.27

1021
CB
TYR
A
343
7.191
31.78
−5.224
1.00
15.76

1022
CG
TYR
A
343
7.085
32.36
−3.832
1.00
18.04

1023
CD1
TYR
A
343
7.013
31.53
−2.715
1.00
19.51

1024
CE1
TYR
A
343
7.059
32.05
−1.422
1.00
20.29

1025
CD2
TYR
A
343
7.191
33.74
−3.626
1.00
19.02

1026
CE2
TYR
A
343
7.245
34.27
−2.339
1.00
20.93

1027
GZ
TYR
A
343
7.183
33.43
−1.244
1.00
20.76

1028
OH
TYR
A
343
7.283
33.95
0.027
1.00
21.61

1029
C
TYR
A
343
8.791
30.72
−6.869
1.00
14.54

1030
O
TYR
A
343
7.847
30.04
−7.289
1.00
15.22

1031
N
GLY
A
344
9.991
30.75
−7.439
1.00
15.09

1032
CA
GLY
A
344
10.308
29.95
−8.61
1.00
16.73

1033
C
GLY
A
344
9.804
30.45
−9.945
1.00
18.37

1034
O
GLY
A
344
9.989
29.78
−10.96
1.00
18.69

1035
N
ASN
A
345
9.187
31.63
−9.969
1.00
18.57

1036
CA
ASN
A
345
8.659
32.13
−11.23
1.00
18.81

1037
CB
ASN
A
345
7.317
32.82
−11
1.00
21.87

1038
CG
ASN
A
345
6.156
31.83
−11
1.00
24.72

1039
OD1
ASN
A
345
5.003
32.23
−10.97
1.00
32.52

1040
ND2
ASN
A
345
6.465
30.55
−11.03
1.00
29.15

1041
C
ASN
A
345
9.596
33.06
−11.99
1.00
18.54

1042
O
ASN
A
345
9.275
33.49
−13.09
1.00
16.73

1043
N
GLY
A
346
10.75
33.34
−11.41
1.00
16.20

1044
CA
GLY
A
346
11.716
34.19
−12.07
1.00
16.52

1045
C
GLY
A
346
13.11
33.64
−11.89
1.00
16.47

1046
O
GLY
A
346
13.336
32.8
−11.01
1.00
15.40

1047
N
PHE
A
347
14.042
34.09
−12.73
1.00
15.82

1048
CA
PHE
A
347
15.435
33.66
−12.65
1.00
15.40

1049
CB
FIfE
A
347
15.719
32.53
−13.65
1.00
16.65

1050
CG
PI1E
A
347
17.154
32.06
−13.64
1.00
20.70

1051
CD1
PHE
A
347
18.106
32.65
−14.48
1.00
19.82

1052
CD2
PI1E
A
347
17.553
31.02
−12.81
1.00
19.54

1053
CE1
PHE
A
347
19.427
32.21
−14.48
1.00
22.34

1054
CE2
PI1E
A
347
18.879
30.57
−12.8
1.00
22.09

1055
CZ
PHE
A
347
19.817
31.17
−13.63
1.00
22.09

1056
C
PHE
A
347
16.261
34.9
−13
1.00
16.41

1057
O
PHE
A
347
16.199
35.4
−14.12
1.00
15.80

1058
N
ILE
A
348
17.012
35.39
−12.02
1.00
14.27

1059
CA
ILE
A
348
17.825
36.58
−12.24
1.00
15.49

1060
CB
ILE
A
348
17.683
37.55
−11.03
1.00
15.76

1061
CG2
ILE
A
348
18.184
36.9
−9.764
1.00
17.30

1062
CG1
ILE
A
348
18.433
38.85
−11.31
1.00
15.24

1063
CD1
ILE
A
348
17.966
40
−10.42
1.00
16.30

1064
C
ILE
A
348
19.272
36.15
−12.46
1.00
16.57

1065
O
ILE
A
348
19.833
35.38
−11.68
1.00
16.99

1066
N
THR
A
349
19.884
36.65
−13.53
1.00
15.69

1067
CA
THR
A
349
21.254
36.24
−13.83
1.00
17.54

1068
CB
THR
A
349
21.628
36.5
−15.32
1.00
18.08

1069
OG1
THR
A
349
21.684
37.91
−15.57
1.00
18.08

1070
CG2
THR
A
349
20.615
35.86
−16.23
1.00
19.40

1071
C
THR
A
349
22.34
36.85
−12.97
1.00
17.79

1072
O
THR
A
349
22.279
38.01
−12.56
1.00
17.03

1073
N
ARG
A
350
23.344
36.02
−12.72
1.00
18.29

1074
CA
ARG
A
350
24.501
36.39
−11.94
1.00
20.41

1075
CB
ARG
A
350
25.467
35.21
−11.91
1.00
20.86

1076
CG
ARG
A
350
26.714
35.44
−11.11
1.00
23.49

1077
CD
ARG
A
350
27.498
34.15
−11.01
1.00
22.29

1078
NE
ARG
A
350
28.617
34.28
−10.09
1.00
25.39

1079
CZ
ARG
A
350
29.426
33.28
−9.755
1.00
25.74

1080
NH1
ARG
A
350
29.237
32.07
−10.26
1.00
25.82

1081
NH2
ARG
A
350
30.417
33.5
−8.906
1.00
25.63

1082
C
ARG
A
350
25.173
37.61
−12.58
1.00
20.85

1083
O
ARG
A
350
25.624
38.52
−11.89
1.00
20.39

1084
N
GLU
A
351
25.226
37.61
−13.91
1.00
21.71

1085
CA
GLU
A
351
25.86
38.71
−14.63
1.00
23.42

1086
CB
GLU
A
351
26.045
38.34
−16.1
1.00
26.93

1087
CG
GLU
A
351
27.152
37.31
−16.32
1.00
31.26

1088
CD
GLU
A
351
28.504
37.81
−15.83
1.00
33.51

1089
OE1
GLU
A
351
28.97
38.86
−16.3
1.00
36.23

1090
0E2
GLU
A
351
29.103
37.14
−14.96
1.00
36.72

1091
C
GLU
A
351
25.106
40.04
−14.51
1.00
21.78

1092
O
GLU
A
351
25.723
41.1
−14.42
1.00
23.51

1093
N
PHE
A
352
23.779
39.98
−14.49
1.00
20.79

1094
CA
PHE
A
352
22.988
41.19
−14.35
1.00
20.13

1095
CB
PHE
A
352
21.496
40.88
−14.53
1.00
21.21

1096
CG
PHE
A
352
20.603
42.07
−14.3
1.00
22.31

1097
CD1
PHE
A
352
20.806
43.26
−14.99
1.00
22.58

1098
CD2
PHE
A
352
19.561
42
−13.38
1.00
22.12

1099
CE1
PHE
A
352
19.985
44.36
−14.77
1.00
22.50

1100
CE2
PHE
A
352
18.734
43.1
−13.15
1.00
21.07

1101
CZ
PHE
A
352
18.947
44.28
−13.85
1.00
23.38

1102
C
PHE
A
352
23.246
41.79
−12.97
1.00
20.06

1103
O
PHE
A
352
23.411
43
−12.82
1.00
18.10

1104
N
LEU
A
353
23.291
40.93
−11.95
1.00
19.09

1105
CA
LEU
A
353
23.537
41.39
−10.6
1.00
19.98

1106
CB
LEU
A
353
23.431
40.22
−9.622
1.00
18.81

1107
CG
LEU
A
353
21.998
39.71
−9.458
1.00
17.36

1108
CD1
LEU
A
353
22.019
38.3
−8.885
1.00
17.66

1109
CD2
LEU
A
353
21.208
40.67
−8.55
1.00
18.64

1110
C
LEU
A
353
24.895
42.08
−10.45
1.00
20.25

1111
O
LEU
A
353
25.003
43.12
−9.792
1.00
20.17

1112
N
LYS
A
354
25.931
41.53
−11.07
1.00
22.58

1113
CA
LYS
A
354
27.248
42.15
−10.97
1.00
25.12

1114
CB
LYS
A
354
28.334
41.15
−11.39
1.00
28.30

1115
CG
LYS
A
354
28.091
40.46
−12.71
1.00
31.49

1116
CD
LYS
A
354
28.929
39.19
−12.83
1.00
34.20

1117
CE
LYS
A
354
30.416
39.46
−12.65
1.00
32.93

1118
NZ
LYS
A
354
31.234
38.26
−12.95
1.00
33.54

1119
C
LYS
A
354
27.349
43.45
−11.77
1.00
26.38

1120
O
LYS
A
354
28.23
44.28
−11.51
1.00
28.05

1121
N
SER
A
355
26.425
43.64
−12.71
1.00
25.99

1122
CA
SER
A
355
26.404
44.84
−13.55
1.00
25.78

1123
CB
SER
A
355
25.604
44.6
−14.83
1.00
27.38

1124
OG
SER
A
355
24.213
44.75
−14.59
1.00
27.61

1125
C
SER
A
355
25.786
46.03
−12.82
1.00
25.54

1126
O
SER
A
355
25.874
47.17
−13.28
1.00
24.80

1127
N
LEU
A
356
25.148
45.76
−11.69
1.00
21.74

1128
CA
LEU
A
356
24.524
46.82
−10.92
1.00
21.47

1129
CB
LEU
A
356
23.682
46.23
−9.789
1.00
20.68

1130
CG
LEU
A
356
22.535
45.31
−10.21
1.00
17.94

1131
CD1
LEU
A
356
21.93
44.68
−8.965
1.00
17.43

1132
CD2
LEU
A
356
21.487
46.11
−10.99
1.00
18.91

1133
C
LEU
A
356
25.576
47.75
−10.34
1.00
22.34

1134
O
LEU
A
356
26.765
47.43
−10.3
1.00
21.32

1135
N
ARG
A
357
25.115
48.9
−9.876
1.00
23.03

1136
CA
ARG
A
357
25.973
49.9
−9.272
1.00
24.90

1137
CB
ARG
A
357
25.177
51.21
−9.192
1.00
26.16

1138
CG
ARG
A
357
25.46
52.09
−7.996
1.00
28.63

1139
CD
ARG
A
357
24.766
53.44
−8.141
1.00
27.93

1140
NE
ARG
A
357
23.501
53.56
−7.416
1.00
25.84

1141
CZ
ARG
A
357
23.381
53.49
−6.094
1.00
25.53

1142
NH1
ARG
A
357
24.449
53.28
−5.332
1.00
26.92

1143
NH2
ARG
A
357
22.199
53.68
−5.527
1.00
26.63

1144
C
ARG
A
357
26.422
49.46
−7.879
1.00
23.21

1145
O
ARG
A
357
25.675
48.78
−7.177
1.00
22.61

1146
N
LYS
A
358
27.646
49.81
−7.483
1.00
23.12

1147
CA
LYS
A
358
28.109
49.46
−6.141
1.00
22.49

1148
CB
LYS
A
358
29.576
49.87
−5.923
1.00
23.58

1149
CG
LYS
A
358
30.609
49.05
−6.695
1.00
22.91

1150
CD
LYS
A
358
32.035
49.59
−6.461
1.00
25.76

1151
CE
LYS
A
358
32.702
48.99
−5.225
1.00
26.68

1152
NZ
LYS
A
358
33.206
47.61
−5.476
1.00
28.29

1153
C
LYS
A
358
27.219
50.27
−5.198
1.00
22.76

1154
O
LYS
A
358
26.764
51.36
−5.548
1.00
24.51

1155
N
PRO
A
359
26.982
49.76
−3.98
1.00
21.69

1156
CD
PRO
A
359
26.263
50.5
−2.93
1.00
23.55

1157
CA
PRO
A
359
27.492
48.49
−3.451
1.00
21.20

1158
CB
PRO
A
359
27.626
48.8
−1.973
1.00
23.13

1159
CG
PRO
A
359
26.366
49.56
−1.719
1.00
22.88

1160
C
PRO
A
359
26.548
47.32
−3.7
1.00
20.65

1161
O
PRO
A
359
26.81
46.19
−3.257
1.00
20.59

1162
N
PHE
A
360
25.454
47.57
−4.404
1.00
19.16

1163
CA
PI1E
A
360
24.473
46.52
−4.671
1.00
18.85

1164
CB
PHE
A
360
23.25
47.14
−5.355
1.00
20.28

1165
CG
PHE
A
360
22.536
48.14
−4.492
1.00
19.94

1166
CD1
PHE
A
360
21.728
47.72
−3.435
1.00
18.19

1167
CD2
PI1E
A
360
22.72
49.51
−4.692
1.00
18.89

1168
CE1
PHE
A
360
21.115
48.65
−2.586
1.00
19.37

1169
CE2
PHE
A
360
22.113
50.43
−3.851
1.00
19.54

1170
CZ
PHE
A
360
21.309
50
−2.794
1.00
19.87

1171
C
PHE
A
360
25.038
45.36
−5.473
1.00
19.99

1172
O
PHE
A
360
24.618
44.21
−5.292
1.00
19.11

1173
N
GYS
A
361
26.009
45.64
−6.338
1.00
17.57

1174
CA
CYS
A
361
26.619
44.58
−7.14
1.00
18.30

1175
CB
CYS
A
361
27.353
45.19
−8.34
1.00
18.99

1176
SG
CYS
A
361
28.657
46.36
−7.884
1.00
20.67

1177
C
CYS
A
361
27.598
43.76
−6.305
1.00
18.14

1178
O
CYS
A
361
28.112
42.75
−6.769
1.00
17.82

1179
N
ASP
A
362
27.837
44.19
−5.068
1.00
18.21

1180
CA
ASP
A
362
28.777
43.48
−4.205
1.00
18.60

1181
CB
ASP
A
362
29.631
44.49
−3.435
1.00
20.06

1182
CG
ASP
A
362
30.428
45.4
−4.359
1.00
20.29

1183
OD1
ASP
A
362
31.017
44.88
−5.319
1.00
21.00

1184
OD2
ASP
A
362
30.464
46.62
−4.121
1.00
22.31

1185
C
ASP
A
362
28.105
42.54
−3.22
1.00
19.14

1186
O
ASP
A
362
28.767
41.93
−2.374
1.00
20.18

1187
N
ILE
A
363
26.791
42.41
−3.344
1.00
17.15

1188
CA
ILE
A
363
26.021
41.56
−2.446
1.00
18.64

1189
CB
ILE
A
363
24.536
42
−2.418
1.00
19.28

1190
CG2
ILE
A
363
23.729
41.06
−1.525
1.00
17.16

1191
CG1
ILE
A
363
24.424
43.44
−1.922
1.00
19.43

1192
CD1
ILE
A
363
23.004
43.98
−1.928
1.00
19.79

1193
C
ILE
A
363
26.039
40.08
−2.781
1.00
18.41

1194
O
ILE
A
363
26.419
39.25
−1.954
1.00
17.58

1195
N
MET
A
364
25.635
39.75
−4.002
1.00
20.04

1196
CA
MET
A
364
25.511
38.35
−4.409
1.00
18.56

1197
CB
MET
A
364
24.434
38.24
−5.491
1.00
19.49

1198
CG
MET
A
364
23.037
38.63
−5.018
1.00
20.24

1199
SD
MET
A
364
22.485
37.68
−3.579
1.00
20.20

1200
CE
MET
A
364
22.609
36.01
−4.236
1.00
16.96

1201
C
MET
A
364
26.706
37.5
−4.823
1.00
18.99

1202
O
MET
A
364
26.654
36.29
−4.644
1.00
17.53

1203
N
GLU
A
365
27.771
38.09
−5.369
1.00
19.55

1204
CA
GLU
A
365
28.91
37.27
−5.794
1.00
19.92

1205
CB
GLU
A
365
30.078
38.13
−6.287
1.00
21.97

1206
CG
GLU
A
365
30.022
38.5
−7.756
1.00
26.26

1207
CD
GLU
A
365
29.832
37.29
−8.656
1.00
27.30

1208
OE1
GLU
A
365
28.693
37.06
−9.104
1.00
26.68

1209
OE2
GLU
A
365
30.817
36.57
−8.909
1.00
29.91

1210
C
GLU
A
365
29.436
36.29
−4.748
1.00
18.52

1211
O
GLU
A
365
29.628
35.11
−5.042
1.00
18.23

1212
N
PRO
A
366
29.689
36.76
−3.516
1.00
18.98

1213
CD
PRO
A
366
29.537
38.13
−2.997
1.00
20.10

1214
CA
PRO
A
366
30.198
35.86
−2.47
1.00
19.09

1215
CB
PRO
A
366
30.29
36.78
−1.251
1.00
20.02

1216
CG
PRO
A
366
30.52
38.14
−1.862
1.00
20.53

1217
C
PRO
A
366
29.278
34.66
−2.211
1.00
17.84

1218
O
PRO
A
366
29.736
33.57
−1.851
1.00
15.96

1219
N
LYS
A
367
27.98
34.88
−2.388
1.00
17.85

1220
CA
LYS
A
367
26.992
33.82
−2.17
1.00
16.69

1221
CB
LYS
A
367
25.603
34.44
−1.964
1.00
17.55

1222
CG
LYS
A
367
25.415
35.17
−0.624
1.00
16.13

1223
CD
LYS
A
367
26.254
36.45
−0.534
1.00
18.57

1224
CE
LYS
A
367
25.819
37.34
0.626
1.00
16.06

1225
NZ
LYS
A
367
26.671
38.58
0.743
1.00
15.29

1226
C
LYS
A
367
26.963
32.84
−3.337
1.00
17.68

1227
O
LYS
A
367
26.783
31.63
−3.142
1.00
17.04

1228
N
PHE
A
368
27.127
33.35
−4.555
1.00
17.39

1229
CA
PHE
A
368
27.156
32.47
−5.719
1.00
16.62

1230
CB
PHE
A
368
27.169
33.28
−7.023
1.00
16.38

1231
CG
PHE
A
368
25.796
33.65
−7.527
1.00
18.08

1232
CD1
PHE
A
368
24.936
32.68
−8.039
1.00
17.39

1233
CD2
PHE
A
368
25.364
34.97
−7.495
1.00
16.89

1234
CE1
PI1E
A
368
23.67
33.02
−8.507
1.00
17.41

1235
CE2
PHE
A
368
24.102
35.32
−7.96
1.00
16.42

1236
CZ
PHE
A
368
23.253
34.35
−8.467
1.00
16.76

1237
C
PHE
A
368
28.426
31.63
−5.6
1.00
16.15

1238
O
PHE
A
368
28.407
30.42
−5.842
1.00
16.24

1239
N
ASP
A
369
29.53
32.26
−5.206
1.00
18.27

1240
CA
ASP
A
369
30.783
31.52
−5.049
1.00
18.69

1241
CB
ASP
A
369
31.952
32.46
−4.709
1.00
20.51

1242
CG
ASP
A
369
32.444
33.24
−5.922
1.00
22.65

1243
OD1
ASP
A
369
32.327
32.72
−7.05
1.00
23.09

1244
OD2
ASP
A
369
32.959
34.36
−5.748
1.00
27.87

1245
C
ASP
A
369
30.638
30.44
−3.979
1.00
18.16

1246
O
ASP
A
369
31.117
29.32
−4.159
1.00
17.43

1247
N
PHE
A
370
29.969
30.76
−2.872
1.00
16.51

1248
CA
PHE
A
370
29.785
29.75
−1.833
1.00
17.11

1249
CB
PHE
A
370
29.146
30.33
−0.571
1.00
17.43

1250
CG
PHE
A
370
28.76
29.28
0.443
1.00
16.12

1251
CD1
PHE
A
370
27.548
28.61
0.339
1.00
15.11

1252
CD2
PHE
A
370
29.643
28.93
1.461
1.00
16.71

1253
CE1
PHE
A
370
27.219
27.58
1.231
1.00
14.11

1254
CE2
PHE
A
370
29.323
27.9
2.356
1.00
15.23

1255
GZ
PHE
A
370
28.109
27.23
2.238
1.00
11.27

1256
C
PHE
A
370
28.902
28.61
−2.342
1.00
16.98

1257
O
PHE
A
370
29.21
27.44
−2.136
1.00
16.87

1258
N
ALA
A
371
27.802
28.97
−2.995
1.00
16.32

1259
CA
ALA
A
371
26.854
27.99
−3.518
1.00
19.25

1260
CB
ALA
A
371
25.659
28.71
−4.147
1.00
17.22

1261
C
ALA
A
371
27.467
27.02
−4.529
1.00
19.60

1262
O
ALA
A
371
27.09
25.85
−4.58
1.00
20.69

1263
N
MET
A
372
28.401
27.51
−5.337
1.00
19.90

1264
CA
MET
A
372
29.029
26.66
−6.342
1.00
23.22

1265
CB
MET
A
372
29.948
27.48
−7.242
1.00
25.16

1266
CG
MET
A
372
29.599
27.38
−8.714
1.00
31.86

1267
SD
MET
A
372
27.844
27.66
−9.043
1.00
35.24

1268
CE
MET
A
372
27.242
26
−9.114
1.00
37.40

1269
C
MET
A
372
29.817
25.54
−5.671
1.00
22.48

1270
O
MET
A
372
29.732
24.38
−6.074
1.00
22.07

1271
N
LYS
A
373
30.577
25.89
−4.641
1.00
21.68

1272
CA
LYS
A
373
31.347
24.88
−3.929
1.00
22.55

1273
CB
LYS
A
373
32.445
25.56
−3.098
1.00
24.59

1274
CG
LYS
A
373
33.599
26.04
−3.977
1.00
28.52

1275
CD
LYS
A
373
34.722
26.71
−3.205
1.00
31.12

1276
CE
LYS
A
373
34.309
28.07
−2.681
1.00
33.08

1277
NZ
LYS
A
373
35.503
28.85
−2.253
1.00
34.91

1278
C
LYS
A
373
30.432
24.02
−3.059
1.00
22.72

1279
O
LYS
A
373
30.685
22.83
−2.874
1.00
22.63

1280
N
PHE
A
374
29.355
24.61
−2.545
1.00
21.24

1281
CA
PHE
A
374
28.425
23.86
−1.708
1.00
20.87

1282
CB
PHE
A
374
27.417
24.79
−1.031
1.00
19.09

1283
CG
PHE
A
374
26.647
24.15
0.097
1.00
19.22

1284
CD1
PHE
A
374
27.258
23.91
1.321
1.00
19.37

1285
CD2
PHE
A
374
25.306
23.81
−0.064
1.00
19.20

1286
CE1
PHE
A
374
26.543
23.33
2.376
1.00
18.07

1287
CE2
PHE
A
374
24.579
23.23
0.98
1.00
18.27

1288
GZ
PHE
A
374
25.2
22.99
2.203
1.00
18.45

1289
C
PHE
A
374
27.667
22.82
−2.536
1.00
20.34

1290
O
PHE
A
374
27.503
21.67
−2.115
1.00
19.46

1291
N
ASN
A
375
27.204
23.23
−3.714
1.00
20.08

1292
CA
ASN
A
375
26.458
22.35
−4.607
1.00
21.22

1293
CB
ASN
A
375
25.903
23.15
−5.791
1.00
21.85

1294
CG
ASN
A
375
24.613
23.89
−5.449
1.00
22.68

1295
ODI
ASN
A
375
24.238
24.85
−6.119
1.00
22.40

1296
ND2
ASN
A
375
23.922
23.42
−4.415
1.00
20.32

1297
C
ASN
A
375
27.322
21.2
−5.119
1.00
21.97

1298
O
ASN
A
375
26.807
20.14
−5.483
1.00
22.05

1299
N
ALA
A
376
28.632
21.41
−5.142
1.00
20.80

1300
CA
ALA
A
376
29.561
20.38
−5.597
1.00
22.52

1301
CB
ALA
A
376
30.974
20.95
−5.677
1.00
22.39

1302
C
ALA
A
376
29.52
19.2
−4.643
1.00
23.80

1303
O
ALA
A
376
30.008
18.11
−4.971
1.00
24.70

1304
N
LEU
A
377
28.943
19.4
−3.459
1.00
22.37

1305
CA
LEU
A
377
28.824
18.34
−2.466
1.00
23.08

1306
CB
LEU
A
377
28.577
18.93
−1.072
1.00
23.25

1307
CG
LEU
A
377
29.719
19.77
−0.485
1.00
23.11

1308
CD1
LEU
A
377
29.376
20.19
0.94
1.00
22.57

1309
CD2
LEU
A
377
31.001
18.95
−0.488
1.00
24.48

1310
C
LEU
A
377
27.686
17.39
−2.833
1.00
22.79

1311
O
LEU
A
377
27.549
16.31
−2.249
1.00
22.44

1312
N
GLU
A
378
26.865
17.8
−3.793
1.00
22.82

1313
CA
GLU
A
378
25.75
16.99
−4.256
1.00
24.48

1314
CB
GLU
A
378
26.291
15.74
−4.949
1.00
26.99

1315
CG
GLU
A
378
26.137
15.73
−6.449
1.00
33.00

1316
CD
GLU
A
378
26.938
14.62
−7.093
1.00
35.36

1317
OE1
GLU
A
378
27.012
13.52
−6.502
1.00
37.48

1318
OE2
GLU
A
378
27.487
14.84
−8.188
1.00
36.92

1319
C
GLU
A
378
24.786
16.57
−3.153
1.00
22.38

1320
O
GLU
A
378
24.3
15.44
−3.142
1.00
23.39

1321
N
LEU
A
379
24.511
17.47
−2.219
1.00
21.57

1322
CA
LEU
A
379
23.589
17.16
−1.134
1.00
18.06

1323
CB
LEU
A
379
23.714
18.18
−0.004
1.00
18.81

1324
CG
LEU
A
379
25.061
18.39
0.688
1.00
16.97

1325
CD1
LEU
A
379
24.863
19.34
1.858
1.00
16.61

1326
GD2
LEU
A
379
25.599
17.06
1.19
1.00
18.25

1327
C
LEU
A
379
22.153
17.19
−1.64
1.00
18.75

1328
O
LEU
A
379
21.855
17.83
−2.651
1.00
19.00

1329
N
ASP
A
380
21.273
16.48
−0.947
1.00
19.17

1330
CA
ASP
A
380
19.862
16.48
−1.296
1.00
18.60

1331
CB
ASP
A
380
19.339
15.06
−1.59
1.00
19.63

1332
CG
ASP
A
380
19.486
14.12
−0.42
1.00
21.42

1333
ODI
ASP
A
380
19.266
14.55
0.728
1.00
18.99

1334
OD2
ASP
A
380
19.801
12.93
−0.657
1.00
24.09

1335
C
ASP
A
380
19.153
17.09
−0.092
1.00
18.66

1336
O
ASP
A
380
19.791
17.39
0.917
1.00
19.31

1337
N
ASP
A
381
17.846
17.28
−0.191
1.00
18.35

1338
CA
ASP
A
381
17.097
17.9
0.894
1.00
18.08

1339
CB
ASP
A
381
15.64
18.08
0.473
1.00
20.09

1340
CG
ASP
A
381
15.489
19.09
−0.658
1.00
21.21

1341
OD1
ASP
A
381
15.934
20.25
−0.482
1.00
20.02

1342
OD2
ASP
A
381
14.932
18.73
−1.719
1.00
22.56

1343
C
ASP
A
381
17.185
17.17
2.234
1.00
17.57

1344
O
ASP
A
381
17.159
17.81
3.284
1.00
17.01

1345
N
SER
A
382
17.297
15.84
2.219
1.00
16.66

1346
CA
SER
A
382
17.403
15.13
3.49
1.00
17.74

1347
CB
SER
A
382
17.364
13.6
3.284
1.00
16.26

1348
OG
SER
A
382
18.502
13.1
2.606
1.00
18.96

1349
G
SER
A
382
18.695
15.55
4.197
1.00
17.27

1350
O
SER
A
382
18.722
15.69
5.419
1.00
19.27

1351
N
ASP
A
383
19.759
15.77
3.427
1.00
16.48

1352
CA
ASP
A
383
21.042
16.2
4.003
1.00
15.88

1353
CB
ASP
A
383
22.172
16.15
2.967
1.00
15.19

1354
CG
ASP
A
383
22.32
14.8
2.306
1.00
18.19

1355
OD1
ASP
A
383
22.365
13.78
3.025
1.00
19.73

1356
OD2
ASP
A
383
22.414
14.78
1.059
1.00
17.35

1357
C
ASP
A
383
20.944
17.64
4.494
1.00
15.34

1358
O
ASP
A
383
21.351
17.96
5.61
1.00
13.16

1359
N
ILE
A
384
20.416
18.5
3.631
1.00
14.16

1360
CA
ILE
A
384
20.279
19.92
3.925
1.00
14.77

1361
CB
ILE
A
384
19.661
20.66
2.712
1.00
14.32

1362
CG2
ILE
A
384
19.454
22.13
3.047
1.00
13.42

1363
CG1
ILE
A
384
20.594
20.52
1.508
1.00
12.81

1364
CD1
ILE
A
384
19.943
20.83
0.161
1.00
10.35

1365
C
ILE
A
384
19.452
20.19
5.18
1.00
15.58

1366
O
ILE
A
384
19.813
21.03
6.001
1.00
15.62

1367
N
SER
A
385
18.355
19.45
5.344
1.00
15.94

1368
CA
SER
A
385
17.513
19.66
6.516
1.00
17.39

1369
CB
SER
A
385
16.323
18.7
6.508
1.00
18.46

1370
OG
SER
A
385
16.747
17.36
6.665
1.00
19.88

1371
C
SER
A
385
18.313
19.48
7.799
1.00
16.76

1372
O
SER
A
385
18.146
20.24
8.735
1.00
15.46

1373
N
LEU
A
386
19.179
18.47
7.841
1.00
17.17

1374
CA
LEU
A
386
19.987
18.22
9.04
1.00
18.15

1375
CB
LEU
A
386
20.649
16.83
8.973
1.00
18.31

1376
CG
LEU
A
386
19.688
15.64
8.899
1.00
20.80

1377
OD1
LEU
A
386
20.461
14.33
8.89
1.00
22.15

1378
CD2
LEU
A
386
18.741
15.68
10.089
1.00
22.01

1379
C
LEU
A
386
21.062
19.29
9.21
1.00
17.32

1380
O
LEU
A
386
21.347
19.72
10.326
1.00
17.55

1381
N
PHE
A
387
21.655
19.7
8.094
1.00
15.68

1382
CA
PHE
A
387
22.701
20.72
8.093
1.00
15.42

1383
CB
PHE
A
387
23.191
20.94
6.658
1.00
14.83

1384
CG
PHE
A
387
24.356
21.88
6.546
1.00
17.91

1385
CD1
PHE
A
387
25.631
21.48
6.933
1.00
18.12

1386
CD2
PHE
A
387
24.174
23.17
6.06
1.00
17.17

1387
CE1
PHE
A
387
26.711
22.36
6.835
1.00
19.84

1388
CE2
PHE
A
387
25.248
24.06
5.96
1.00
17.27

1389
CZ
PHE
A
387
26.519
23.64
6.349
1.00
18.98

1390
C
PHE
A
387
22.14
22.03
8.667
1.00
14.65

1391
O
PHE
A
387
22.78
22.7
9.488
1.00
14.80

1392
N
VAL
A
388
20.937
22.4
8.235
1.00
14.52

1393
CA
VAL
A
388
20.302
23.62
8.715
1.00
13.14

1394
CB
VAL
A
388
19.061
23.96
7.856
1.00
14.31

1395
CG1
VAL
A
388
18.253
25.08
8.481
1.00
13.46

1396
CG2
VAL
A
388
19.531
24.38
6.456
1.00
13.68

1397
C
VAL
A
388
19.941
23.53
10.205
1.00
14.97

1398
O
VAL
A
388
20.1
24.5
10.946
1.00
14.16

1399
N
ALA
A
389
19.468
22.37
10.651
1.00
14.60

1400
CA
ALA
A
389
19.132
22.21
12.068
1.00
15.75

1401
CB
ALA
A
389
18.534
20.83
12.333
1.00
14.49

1402
C
ALA
A
389
20.409
22.39
12.884
1.00
17.48

1403
O
ALA
A
389
20.39
22.96
13.974
1.00
18.76

1404
N
ALA
A
390
21.516
21.89
12.345
1.00
17.47

1405
CA
ALA
A
390
22.806
21.99
13.012
1.00
18.52

1406
CB
ALA
A
390
23.838
21.13
12.278
1.00
18.08

1407
C
ALA
A
390
23.295
23.44
13.117
1.00
18.95

1408
O
ALA
A
390
23.835
23.84
14.146
1.00
18.98

1409
N
ILE
A
391
23.113
24.24
12.069
1.00
18.97

1410
CA
ILE
A
391
23.579
25.62
12.165
1.00
19.61

1411
CB
ILE
A
391
23.595
26.35
10.777
1.00
22.32

1412
CG2
ILE
A
391
24.049
25.41
9.693
1.00
22.00

1413
CG1
ILE
A
391
22.233
26.94
10.455
1.00
25.81

1414
CD1
ILE
A
391
22.036
28.31
11.06
1.00
26.92

1415
C
ILE
A
391
22.718
26.41
13.158
1.00
19.24

1416
O
ILE
A
391
23.218
27.27
13.876
1.00
18.21

1417
N
ILE
A
392
21.429
26.09
13.212
1.00
17.90

1418
CA
ILE
A
392
20.514
26.77
14.118
1.00
18.91

1419
CB
ILE
A
392
19.047
26.43
13.79
1.00
20.25

1420
CG2
ILE
A
392
18.119
26.92
14.901
1.00
20.50

1421
CG1
ILE
A
392
18.658
27.05
12.449
1.00
19.74

1422
CD1
ILE
A
392
17.232
26.77
12.028
1.00
20.27

1423
C
ILE
A
392
20.785
26.43
15.583
1.00
19.83

1424
O
11E
A
392
20.872
27.32
16.435
1.00
18.98

1425
N
CYS
A
393
20.935
25.15
15.874
1.00
21.71

1426
CA
CYS
A
393
21.175
24.73
17.249
1.00
24.63

1427
CB
CYS
A
393
20.59
23.34
17.457
1.00
26.05

1428
SG
CYS
A
393
18.833
23.3
17.09
1.00
27.14

1429
C
CYS
A
393
22.655
24.76
17.576
1.00
25.29

1430
O
CYS
A
393
23.279
23.73
17.837
1.00
26.58

1431
N
CYS
A
394
23.196
25.97
17.561
1.00
27.00

1432
CA
CYS
A
394
24.602
26.23
17.818
1.00
28.30

1433
CB
CYS
A
394
25.095
27.25
16.792
1.00
30.14

1434
SG
CYS
A
394
26.804
27.71
16.962
1.00
32.84

1435
C
CYS
A
394
24.818
26.77
19.237
1.00
27.82

1436
O
CYS
A
394
24.279
27.82
19.602
1.00
27.12

1437
N
GLY
A
395
25.619
26.06
20.025
1.00
28.23

1438
CA
GLY
A
395
25.869
26.48
21.394
1.00
28.09

1439
C
GLY
A
395
26.924
27.55
21.575
1.00
28.17

1440
O
GLY
A
395
27.155
28.01
22.693
1.00
30.05

1441
N
ASP
A
396
27.556
27.97
20.483
1.00
29.00

1442
CA
ASP
A
396
28.603
28.98
20.54
1.00
29.78

1443
CB
ASP
A
396
29.678
28.7
19.49
1.00
33.93

1444
CG
ASP
A
396
30.174
27.28
19.544
1.00
37.57

1445
OD1
ASP
A
396
30.417
26.78
20.664
1.00
40.66

1446
OD2
ASP
A
396
30.329
26.66
18.466
1.00
39.44

1447
C
ASP
A
396
28.108
30.41
20.326
1.00
27.38

1448
O
ASP
A
396
28.888
31.35
20.404
1.00
27.02

1449
N
ARG
A
397
26.821
30.57
20.046
1.00
25.37

1450
CA
ARG
A
397
26.27
31.89
19.804
1.00
24.60

1451
CB
ARG
A
397
24.784
31.79
19.463
1.00
23.34

1452
CG
ARG
A
397
24.477
30.85
18.313
1.00
19.60

1453
CD
ARG
A
397
25.267
31.21
17.066
1.00
20.49

1454
NE
ARG
A
397
24.765
30.48
15.905
1.00
14.79

1455
CZ
ARG
A
397
25.326
30.5
14.703
1.00
16.61

1456
NH1
ARG
A
397
26.427
31.22
14.486
1.00
14.39

1457
NH2
ARG
A
397
24.786
29.8
13.717
1.00
14.57

1458
C
ARG
A
397
26.456
32.84
20.985
1.00
26.30

1459
O
ARG
A
397
26.283
32.45
22.14
1.00
26.77

1460
N
PRO
A
398
26.822
34.1
20.704
1.00
27.02

1461
CD
PRO
A
398
27.21
34.63
19.386
1.00
26.91

1462
CA
PRO
A
398
27.026
35.1
21.752
1.00
27.46

1463
CB
PRO
A
398
27.449
36.34
20.964
1.00
28.18

1464
CG
PRO
A
398
28.124
35.77
19.765
1.00
28.30

1465
C
PRO
A
398
25.735
35.35
22.534
1.00
28.08

1466
O
PRO
A
398
24.643
35.27
21.975
1.00
28.60

1467
N
GLY
A
399
25.872
35.63
23.826
1.00
27.99

1468
CA
GLY
A
399
24.716
35.92
24.66
1.00
27.31

1469
C
GLY
A
399
23.795
34.79
25.072
1.00
26.48

1470
O
GLY
A
399
22.714
35.04
25.603
1.00
25.44

1471
N
LEU
A
400
24.197
33.54
24.833
1.00
25.96

1472
CA
LEU
A
400
23.365
32.4
25.209
1.00
26.11

1473
CB
LEU
A
400
23.807
31.14
24.474
1.00
26.09

1474
CG
LEU
A
400
23.406
30.99
23.006
1.00
25.05

1475
CD1
LEU
A
400
24.037
29.73
22.44
1.00
23.61

1476
CD2
LEU
A
400
21.892
30.93
22.889
1.00
23.97

1477
C
LEU
A
400
23.431
32.14
26.706
1.00
27.86

1478
O
LEU
A
400
24.473
32.34
27.334
1.00
26.88

1479
N
LEU
A
401
22.318
31.67
27.261
1.00
28.14

1480
CA
LEU
A
401
22.233
31.38
28.684
1.00
31.00

1481
CB
LEU
A
401
20.865
31.8
29.228
1.00
30.68

1482
CG
LEU
A
401
20.578
31.45
30.691
1.00
32.59

1483
CD1
LEU
A
401
21.62
32.1
31.597
1.00
32.90

1484
CD2
LEU
A
401
19.179
31.92
31.06
1.00
31.69

1485
C
LEU
A
401
22.429
29.89
28.943
1.00
31.60

1486
O
LEU
A
401
23.369
29.48
29.622
1.00
33.05

1487
N
ASN
A
402
21.532
29.09
28.383
1.00
31.62

1488
CA
ASN
A
402
21.56
27.65
28.559
1.00
32.32

1489
CB
ASN
A
402
20.142
27.12
28.394
1.00
34.00

1490
CG
ASN
A
402
19.94
25.79
29.062
1.00
36.18

1491
OD1
ASN
A
402
18.817
25.3
29.135
1.00
38.80

1492
ND2
ASN
A
402
21.022
25.2
29.558
1.00
37.30

1493
C
ASN
A
402
22.508
26.95
27.584
1.00
31.82

1494
O
ASN
A
402
22.123
25.98
26.925
1.00
30.71

1495
N
VAL
A
403
23.746
27.42
27.514
1.00
31.16

1496
CA
VAL
A
403
24.752
26.85
26.624
1.00
31.48

1497
CB
VAL
A
403
26.143
27.48
26.903
1.00
31.26

1498
CG1
VAL
A
403
26.484
27.35
28.377
1.00
32.59

1499
CG2
VAL
A
403
27.211
26.82
26.045
1.00
31.72

1500
C
VAL
A
403
24.847
25.32
26.73
1.00
31.80

1501
O
VAL
A
403
24.987
24.63
25.72
1.00
32.39

1502
N
GLY
A
404
24.756
24.8
27.949
1.00
30.80

1503
CA
GLY
A
404
24.836
23.36
28.141
1.00
30.87

1504
C
GLY
A
404
23.746
22.57
27.442
1.00
31.11

1505
O
GLY
A
404
24.032
21.62
26.71
1.00
31.28

1506
N
HIS
A
405
22.493
22.95
27.661
1.00
30.39

1507
CA
HIS
A
405
21.37
22.26
27.051
1.00
30.64

1508
CB
HIS
A
405
20.045
22.78
27.623
1.00
33.97

1509
CG
HIS
A
405
19.876
22.51
29.09
1.00
38.64

1510
CD2
HIS
A
405
18.885
22.85
29.952
1.00
40.99

1511
ND1
HIS
A
405
20.82
21.84
29.836
1.00
39.58

1512
CE1
HIS
A
405
20.42
21.77
31.094
1.00
41.27

1513
NE2
HIS
A
405
19.25
22.38
31.191
1.00
41.61

1514
C
HIS
A
405
21.385
22.38
25.53
1.00
29.36

1515
O
HIS
A
405
20.963
21.47
24.827
1.00
28.36

1516
N
ILE
A
406
21.881
23.5
25.024
1.00
27.89

1517
CA
ILE
A
406
21.943
23.71
23.58
1.00
27.60

1518
CB
ILE
A
406
22.21
25.19
23.238
1.00
25.64

1519
CG2
ILE
A
406
22.473
25.36
21.741
1.00
25.46

1520
CG1
ILE
A
406
20.993
26.03
23.636
1.00
23.43

1521
CD1
ILE
A
406
21.23
27.53
23.575
1.00
23.81

1522
C
ILE
A
406
23.023
22.82
22.961
1.00
28.42

1523
O
ILE
A
406
22.848
22.3
21.86
1.00
28.52

1524
N
GLU
A
407
24.132
22.63
23.673
1.00
28.38

1525
CA
GLU
A
407
25.21
21.79
23.165
1.00
30.86

1526
CB
GLU
A
407
26.435
21.85
24.087
1.00
31.87

1527
CG
GLU
A
407
27.059
23.22
24.208
1.00
35.51

1528
CD
GLU
A
407
28.343
23.21
25.016
1.00
37.24

1529
OE1
GLU
A
407
28.346
22.62
26.121
1.00
38.47

1530
OE2
GLU
A
407
29.345
23.79
24.548
1.00
39.11

1531
C
GLU
A
407
24.754
20.34
23.033
1.00
30.96

1532
O
GLU
A
407
25.116
19.65
22.081
1.00
32.65

1533
N
LYS
A
408
23.959
19.87
23.991
1.00
31.74

1534
CA
LYS
A
408
23.47
18.49
23.962
1.00
32.12

1535
CB
LYS
A
408
22.748
18.16
25.275
1.00
34.57

1536
CG
LYS
A
408
21.294
18.6
25.333
1.00
37.40

1537
CD
LYS
A
408
20.363
17.48
24.898
1.00
39.89

1538
CE
LYS
A
408
19.082
18.02
24.279
1.00
40.38

1539
NZ
LYS
A
408
18.438
19.07
25.118
1.00
42.06

1540
C
LYS
A
408
22.527
18.33
22.771
1.00
30.88

1541
O
LYS
A
408
22.44
17.26
22.168
1.00
29.64

1542
N
MET
A
409
21.827
19.41
22.436
1.00
30.20

1543
CA
MET
A
409
20.907
19.4
21.304
1.00
30.04

1544
CB
MET
A
409
20.125
20.71
21.259
1.00
31.30

1545
CG
MET
A
409
18.627
20.56
21.382
1.00
34.42

1546
SD
MET
A
409
17.79
22.14
21.137
1.00
37.50

1547
CE
MET
A
409
17.603
22.66
22.784
1.00
35.32

1548
C
MET
A
409
21.703
19.25
20.01
1.00
28.14

1549
O
MET
A
409
21.397
18.4
19.172
1.00
27.06

1550
N
GLN
A
410
22.726
20.09
19.851
1.00
27.24

1551
CA
GLN
A
410
23.555
20.04
18.652
1.00
27.85

1552
CB
GLN
A
410
24.58
21.19
18.647
1.00
29.46

1553
CG
GLN
A
410
25.441
21.21
17.38
1.00
32.43

1554
CD
GLN
A
410
26.288
22.47
17.245
1.00
34.32

1555
OE1
GLN
A
410
27.097
22.79
18.115
1.00
34.44

1556
NE2
GLN
A
410
26.105
23.19
16.14
1.00
32.43

1557
C
GLN
A
410
24.275
18.71
18.545
1.00
27.48

1558
O
GLN
A
410
24.483
18.19
17.449
1.00
26.07

1559
N
GLU
A
411
24.645
18.14
19.691
1.00
27.34

1560
CA
GLU
A
411
25.339
16.86
19.731
1.00
28.25

1561
CB
GLU
A
411
25.621
16.46
21.186
1.00
30.37

1562
CG
GLU
A
411
26.281
15.09
21.341
1.00
35.80

1563
CD
GLU
A
411
26.58
14.74
22.791
1.00
38.57

1564
OE1
GLU
A
411
27.532
15.32
23.359
1.00
39.33

1565
OE2
GLU
A
411
25.858
13.89
23.364
1.00
39.79

1566
C
GLU
A
411
24.508
15.78
19.043
1.00
26.37

1567
O
GLU
A
411
25.022
15.03
18.213
1.00
26.12

1568
N
GLY
A
412
23.226
15.71
19.396
1.00
22.95

1569
CA
GLY
A
412
22.335
14.73
18.811
1.00
22.23

1570
C
GLY
A
412
22.12
14.94
17.323
1.00
22.14

1571
O
GLY
A
412
22.074
13.99
16.55
1.00
22.69

1572
N
ILE
A
413
21.984
16.2
16.918
1.00
20.27

1573
CA
ILE
A
413
21.785
16.53
15.507
1.00
20.28

1574
CB
ILE
A
413
21.5
18.06
15.334
1.00
18.92

1575
CG2
ILE
A
413
21.591
18.46
13.857
1.00
18.08

1576
CG1
ILE
A
413
20.124
18.38
15.919
1.00
20.64

1577
CD1
ILE
A
413
19.761
19.87
15.944
1.00
21.12

1578
C
ILE
A
413
23.01
16.13
14.686
1.00
20.45

1579
O
ILE
A
413
22.886
15.5
13.637
1.00
19.39

1580
N
VAL
A
414
24.191
16.49
15.177
1.00
22.04

1581
CA
VAL
A
414
25.438
16.16
14.493
1.00
24.01

1582
CB
VAL
A
414
26.648
16.76
15.237
1.00
24.63

1583
CG1
VAL
A
414
27.944
16.24
14.633
1.00
26.70

1584
CG2
VAL
A
414
26.604
18.28
15.152
1.00
25.08

1585
C
VAL
A
414
25.621
14.66
14.382
1.00
24.35

1586
O
VAL
A
414
26.059
14.15
13.352
1.00
24.50

1587
N
HIS
A
415
25.289
13.95
15.457
1.00
24.73

1588
CA
HIS
A
415
25.398
12.5
15.496
1.00
25.40

1589
CB
HIS
A
415
24.877
11.98
16.836
1.00
27.91

1590
CG
HIS
A
415
24.706
10.49
16.882
1.00
29.97

1591
CD2
HIS
A
415
23.603
9.718
16.752
1.00
31.72

1592
ND1
HIS
A
415
25.765
9.623
17.036
1.00
32.64

1593
CE1
HIS
A
415
25.321
8.379
16.999
1.00
31.24

1594
NE2
HIS
A
415
24.013
8.408
16.826
1.00
32.29

1595
C
HIS
A
415
24.576
11.89
14.363
1.00
24.78

1596
O
HIS
A
415
25.076
11.09
13.57
1.00
23.70

1597
N
VAL
A
416
23.308
12.29
14.302
1.00
24.16

1598
CA
VAL
A
416
22.393
11.8
13.28
1.00
24.60

1599
CB
VAL
A
416
20.96
12.32
13.548
1.00
26.47

1600
CG1
VAL
A
416
20.056
12.01
12.371
1.00
29.88

1601
CG2
VAL
A
416
20.411
11.66
14.809
1.00
27.86

1602
C
VAL
A
416
22.868
12.22
11.889
1.00
23.32

1603
O
VAL
A
416
22.743
11.46
10.927
1.00
21.28

1604
N
LEU
A
417
23.43
13.42
11.788
1.00
21.40

1605
CA
LEU
A
417
23.936
13.92
10.512
1.00
20.88

1606
CB
LEU
A
417
24.389
15.38
10.638
1.00
20.25

1607
CG
LEU
A
417
25.166
15.98
9.461
1.00
19.60

1608
CD1
LEU
A
417
24.323
15.92
8.189
1.00
18.77

1609
CD2
LEU
A
417
25.549
17.41
9.782
1.00
20.66

1610
C
LEU
A
417
25.103
13.06
10.031
1.00
21.76

1611
O
LEU
A
417
25.134
12.64
8.877
1.00
21.23

1612
N
ARG
A
418
26.056
12.78
10.921
1.00
22.31

1613
CA
ARG
A
418
27.214
11.97
10.551
1.00
23.13

1614
CB
ARG
A
418
28.166
11.78
11.738
1.00
25.75

1615
CG
ARG
A
418
29.481
11.11
11.325
1.00
30.84

1616
CD
ARG
A
418
30.375
10.73
12.502
1.00
34.64

1617
NE
ARG
A
418
30.554
11.83
13.446
1.00
36.72

1618
CZ
ARG
A
418
29.916
11.92
14.608
1.00
38.12

1619
NH1
ARG
A
418
29.061
10.98
14.969
1.00
40.03

1620
NH2
ARG
A
418
30.131
12.96
15.406
1.00
40.43

1621
C
ARG
A
418
26.795
10.6
10.036
1.00
23.39

1622
O
ARG
A
418
27.332
10.11
9.043
1.00
22.61

1623
N
LEU
A
419
25.837
9.988
10.721
1.00
22.60

1624
CA
LEU
A
419
25.35
8.67
10.333
1.00
24.37

1625
CB
LEU
A
419
24.453
8.101
11.439
1.00
24.59

1626
CG
LEU
A
419
25.209
7.675
12.708
1.00
27.68

1627
CDL
LEU
A
419
24.232
7.27
13.802
1.00
27.24

1628
CD2
LEU
A
419
26.141
6.522
12.37
1.00
26.90

1629
C
LEU
A
419
24.594
8.736
9.007
1.00
23.58

1630
O
LEU
A
419
24.753
7.87
8.141
1.00
22.71

1631
N
HIS
A
420
23.782
9.772
8.845
1.00
22.55

1632
CA
HIS
A
420
23.011
9.943
7.619
1.00
22.81

1633
CB
HIS
A
420
22.098
11.17
7.748
1.00
22.24

1634
CG
HIS
A
420
21.152
11.34
6.6
1.00
22.11

1635
CD2
HIS
A
420
19.934
10.8
6.361
1.00
23.05

1636
NDL
HIS
A
420
21.435
12.14
5.51
1.00
23.65

1637
CE1
HIS
A
420
20.435
12.08
4.649
1.00
20.84

1638
NE2
HIS
A
420
19.512
11.27
5.141
1.00
24.45

1639
C
HIS
A
420
23.929
10.09
6.407
1.00
22.74

1640
O
HIS
A
420
23.687
9.488
5.355
1.00
21.42

1641
N
LEU
A
421
24.985
10.89
6.553
1.00
20.60

1642
CA
LEU
A
421
25.926
11.09
5.458
1.00
22.09

1643
CB
LEU
A
421
26.967
12.15
5.837
1.00
21.12

1644
CG
LEU
A
421
26.44
13.58
6.022
1.00
20.72

1645
CD1
LEU
A
421
27.573
14.49
6.475
1.00
20.64

1646
CD2
LEU
A
421
25.832
14.07
4.708
1.00
21.54

1647
C
LEU
A
421
26.636
9.806
5.062
1.00
22.50

1648
O
LEU
A
421
26.916
9.584
3.885
1.00
22.76

1649
N
GLN
A
422
26.941
8.962
6.042
1.00
24.45

1650
CA
GLN
A
422
27.621
7.706
5.75
1.00
26.41

1651
CB
GLN
A
422
28.016
6.992
7.047
1.00
28.87

1652
CG
GLN
A
422
29.241
7.583
7.717
1.00
32.50

1653
CD
GLN
A
422
30.157
6.52
8.293
1.00
31.70

1654
OE1
GLN
A
422
29.819
5.852
9.27
1.00
36.19

1655
NE2
GLN
A
422
31.325
6.353
7.68
1.00
38.34

1656
C
GLN
A
422
26.765
6.781
4.888
1.00
26.96

1657
O
GLN
A
422
27.271
6.136
3.968
1.00
26.69

1658
N
SER
A
423
25.468
6.729
5.176
1.00
26.98

1659
CA
SER
A
423
24.555
5.88
4.417
1.00
27.71

1660
CB
SER
A
423
23.377
5.458
5.298
1.00
29.19

1661
OG
SER
A
423
22.558
6.566
5.623
1.00
33.45

1662
C
SER
A
423
24.02
6.524
3.137
1.00
26.94

1663
O
SER
A
423
23.724
5.825
2.17
1.00
27.54

1664
N
ASN
A
424
23.892
7.851
3.124
1.00
25.54

1665
CA
ASN
A
424
23.371
8.557
1.947
1.00
24.76

1666
CB
ASN
A
424
22.674
9.86
2.377
1.00
24.73

1667
CG
ASN
A
424
21.705
10.4
1.318
1.00
26.54

1668
OD1
ASN
A
424
21.319
11.57
1.348
1.00
25.37

1669
ND2
ASN
A
424
21.295
9.532
0.392
1.00
24.83

1670
C
ASN
A
424
24.468
8.873
0.928
1.00
24.23

1671
O
ASN
A
424
24.201
8.95
−0.271
1.00
23.51

1672
N
HIS
A
425
25.698
9.06
1.405
1.00
23.19

1673
CA
HIS
A
425
26.833
9.36
0.53
1.00
24.23

1674
CB
HIS
A
425
27.272
10.83
0.682
1.00
22.51

1675
CG
HIS
A
425
26.239
11.82
0.242
1.00
21.91

1676
CD2
HIS
A
425
26.002
12.38
−0.967
1.00
19.28

1677
ND1
HIS
A
425
25.284
12.33
1.096
1.00
22.80

1678
CE1
HIS
A
425
24.503
13.16
0.431
1.00
17.33

1679
NE2
HIS
A
425
24.917
13.21
−0.823
1.00
20.76

1680
C
HIS
A
425
28.016
8.451
0.862
1.00
26.11

1681
O
HIS
A
425
29.073
8.918
1.285
1.00
24.94

1682
N
PRO
A
426
27.856
7.136
0.65
1.00
29.11

1683
CD
PRO
A
426
26.708
6.467
0.008
1.00
29.49

1684
CA
PRO
A
426
28.922
6.174
0.94
1.00
30.85

1685
CB
PRO
A
426
28.248
4.831
0.67
1.00
31.26

1686
CG
PRO
A
426
27.321
5.157
−0.46
1.00
30.77

1687
C
PRO
A
426
30.193
6.361
0.119
1.00
33.62

1688
O
PRO
A
426
31.268
5.919
0.529
1.00
35.12

1689
N
ASP
A
427
30.08
7.013
−1.034
1.00
34.60

1690
CA
ASP
A
427
31.243
7.22
−1.883
1.00
36.67

1691
CB
ASP
A
427
30.827
7.268
−3.357
1.00
39.63

1692
CG
ASP
A
427
30.146
5.986
−3.814
1.00
41.06

1693
OD1
ASP
A
427
30.565
4.897
−3.366
1.00
42.57

1694
OD2
ASP
A
427
29.201
6.068
−4.629
1.00
43.11

1695
C
ASP
A
427
32.053
8.465
−1.542
1.00
37.42

1696
O
ASP
A
427
33.263
8.498
−1.774
1.00
37.62

1697
N
ASP
A
428
31.402
9.486
−0.99
1.00
37.02

1698
CA
ASP
A
428
32.126
10.71
−0.649
1.00
37.69

1699
CB
ASP
A
428
31.198
11.9
−0.46
1.00
36.87

1700
CG
ASP
A
428
31.972
13.21
−0.347
1.00
37.47

1701
OD1
ASP
A
428
33.072
13.21
0.248
1.00
36.42

1702
OD2
ASP
A
428
31.484
14.25
−0.847
1.00
37.98

1703
C
ASP
A
428
32.96
10.55
0.602
1.00
38.20

1704
O
ASP
A
428
32.451
10.39
1.714
1.00
37.99

1705
N
ILE
A
429
34.261
10.63
0.385
1.00
39.15

1706
CA
ILE
A
429
35.269
10.51
1.414
1.00
37.95

1707
CB
ILE
A
429
36.628
10.91
0.814
1.00
39.91

1708
CG2
ILE
A
429
37.047
9.889
−0.236
1.00
40.60

1709
OG1
ILE
A
429
36.508
12.29
0.139
1.00
41.10

1710
CD1
ILE
A
429
37.785
12.79
−0.515
1.00
42.96

1711
C
ILE
A
429
35.027
11.31
2.702
1.00
35.07

1712
O
ILE
A
429
34.534
10.78
3.698
1.00
35.43

1713
N
PHE
A
430
35.379
12.58
2.67
1.00
31.63

1714
CA
PHE
A
430
35.263
13.44
3.831
1.00
26.48

1715
CB
PHE
A
430
36.493
14.35
3.926
1.00
29.04

1716
CG
PHE
A
430
37.806
13.62
3.916
1.00
30.93

1717
CD1
PHE
A
430
38.349
13.15
2.729
1.00
33.42

1718
GD2
PHE
A
430
38.518
13.44
5.093
1.00
31.75

1719
CE1
PHE
A
430
39.592
12.51
2.714
1.00
34.29

1720
CE2
PHE
A
430
39.758
12.8
5.091
1.00
31.88

1721
CZ
PHE
A
430
40.296
12.34
3.9
1.00
33.09

1722
C
PHE
A
430
34.035
14.34
3.817
1.00
23.47

1723
O
PHE
A
430
34.15
15.51
4.167
1.00
21.09

1724
N
LEU
A
431
32.864
13.83
3.444
1.00
20.27

1725
CA
LEU
A
431
31.7
14.72
3.403
1.00
17.44

1726
CB
LEU
A
431
30.468
13.98
2.853
1.00
15.99

1727
CG
LEU
A
431
29.23
14.85
2.603
1.00
14.82

1728
CD1
LEU
A
431
29.603
16.1
1.815
1.00
15.78

1729
CD2
LEU
A
431
28.183
14.05
1.862
1.00
16.91

1730
C
LEU
A
431
31.378
15.38
4.747
1.00
17.17

1731
O
LEU
A
431
31
16.56
4.789
1.00
15.16

1732
N
PHE
A
432
31.533
14.65
5.852
1.00
15.85

1733
CA
PHE
A
432
31.243
15.25
7.156
1.00
15.61

1734
CB
PUB
A
432
31.332
14.19
8.267
1.00
17.14

1735
CO
PHE
A
432
30.971
14.71
9.629
1.00
18.64

1736
CD1
PUB
A
432
29.695
15.2
9.889
1.00
20.33

1737
CD2
PHE
A
432
31.906
14.71
10.657
1.00
20.31

1738
CE1
PHE
A
432
29.355
15.68
11.157
1.00
20.29

1739
CE2
PUB
A
432
31.576
15.18
11.93
1.00
21.44

1740
CZ
PHE
A
432
30.299
15.67
12.179
1.00
22.31

1741
C
PHE
A
432
32.196
16.41
7.451
1.00
16.28

1742
O
PHE
A
432
31.754
17.54
7.719
1.00
14.24

1743
N
PRO
A
433
33.52
16.17
7.422
1.00
17.45

1744
CD
PRO
A
433
34.282
14.91
7.339
1.00
17.91

1745
CA
PRO
A
433
34.396
17.31
7.704
1.00
16.84

1746
CB
PRO
A
433
35.796
16.68
7.766
1.00
19.13

1747
CO
PRO
A
433
35.663
15.4
6.995
1.00
18.96

1748
C
PRO
A
433
34.255
18.44
6.663
1.00
15.92

1749
O
PRO
A
433
34.466
19.61
6.974
1.00
15.44

1750
N
LYS
A
434
33.882
18.08
5.435
1.00
16.05

1751
CA
LYS
A
434
33.678
19.1
4.401
1.00
15.22

1752
CB
LYS
A
434
33.261
18.45
3.076
1.00
15.46

1753
CG
LYS
A
434
34.363
17.72
2.337
1.00
16.19

1754
CD
LYS
A
434
33.806
17.12
1.056
1.00
17.44

1755
CE
LYS
A
434
34.848
16.33
0.281
1.00
19.89

1756
NZ
LYS
A
434
34.259
15.78
−0.979
1.00
18.37

1757
C
LYS
A
434
32.561
20.03
4.857
1.00
14.66

1758
O
LYS
A
434
32.659
21.26
4.722
1.00
13.26

1759
N
LEU
A
435
31.495
19.45
5.397
1.00
13.97

1760
CA
LEU
A
435
30.351
20.22
5.869
1.00
14.01

1761
CB
LEU
A
435
29.154
19.31
6.134
1.00
14.60

1762
CG
LEU
A
435
28.489
18.73
4.885
1.00
18.11

1763
CD1
LEU
A
435
27.366
17.78
5.291
1.00
19.14

1764
CD2
LEU
A
435
27.947
19.86
4.019
1.00
19.11

1765
C
LEU
A
435
30.695
21.02
7.118
1.00
15.51

1766
O
LEU
A
435
30.2
22.14
7.303
1.00
16.69

1767
N
LEU
A
436
31.546
20.47
7.977
1.00
16.13

1768
CA
LEU
A
436
31.947
21.22
9.163
1.00
17.20

1769
CB
LEU
A
436
32.875
20.39
10.053
1.00
19.20

1770
CG
LEU
A
436
32.224
19.18
10.73
1.00
21.00

1771
CD1
LEU
A
436
33.252
18.44
11.581
1.00
22.86

1772
CD2
LEU
A
436
31.057
19.64
11.589
1.00
22.35

1773
C
LEU
A
436
32.667
22.47
8.693
1.00
17.44

1774
O
LEU
A
436
32.488
23.55
9.265
1.00
15.95

1775
N
GLN
A
437
33.481
22.35
7.647
1.00
16.16

1776
CA
GLN
A
437
34.183
23.53
7.137
1.00
16.84

1777
CB
GLN
A
437
35.235
23.15
6.09
1.00
17.05

1778
CG
GLN
A
437
36.012
24.37
5.576
1.00
20.71

1779
CD
GLN
A
437
36.985
24.04
4.46
1.00
22.77

1780
OE1
GLN
A
437
36.622
23.4
3.475
1.00
25.06

1781
NE2
GLN
A
437
38.227
24.5
4.604
1.00
26.03

1782
C
GLN
A
437
33.179
24.51
6.529
1.00
17.18

1783
O
GLN
A
437
33.329
25.72
6.668
1.00
17.33

1784
N
LYS
A
438
32.15
23.99
5.858
1.00
17.54

1785
CA
LYS
A
438
31.136
24.87
5.262
1.00
17.07

1786
CB
LYS
A
438
30.083
24.06
4.502
1.00
17.70

1787
CG
LYS
A
438
30.623
23.31
3.309
1.00
19.51

1788
CD
LYS
A
438
31.345
24.23
2.341
1.00
22.06

1789
CE
LYS
A
438
31.902
23.44
1.155
1.00
22.64

1790
NZ
LYS
A
438
32.819
24.28
0.343
1.00
21.64

1791
C
LYS
A
438
30.443
25.7
6.329
1.00
18.54

1792
O
LYS
A
438
30.07
26.85
6.084
1.00
16.97

1793
N
MET
A
439
30.257
25.12
7.512
1.00
18.74

1794
CA
MET
A
439
29.619
25.85
8.599
1.00
19.35

1795
CB
MET
A
439
29.426
24.95
9.814
1.00
22.86

1796
CG
MET
A
439
28.564
23.73
9.519
1.00
25.60

1797
SD
MET
A
439
28.191
22.76
10.972
1.00
29.86

1798
CE
MET
A
439
26.648
23.51
11.476
1.00
30.44

1799
C
MET
A
439
30.503
27.04
8.97
1.00
19.48

1800
O
MET
A
439
30.009
28.13
9.217
1.00
17.93

1801
N
ALA
A
440
31.815
26.82
9.007
1.00
19.56

1802
CA
ALA
A
440
32.762
27.88
9.34
1.00
18.57

1803
CB
ALA
A
440
34.153
27.29
9.549
1.00
20.87

1804
C
ALA
A
440
32.796
28.93
8.232
1.00
19.19

1805
O
ALA
A
440
32.903
30.13
8.496
1.00
18.72

1806
N
ASP
A
441
32.713
28.47
6.987
1.00
17.33

1807
CA
ASP
A
441
32.722
29.38
5.848
1.00
17.47

1808
CB
ASP
A
441
32.749
28.6
4.533
1.00
18.81

1809
CG
ASP
A
441
34.084
27.92
4.279
1.00
22.11

1810
OD1
ASP
A
441
35.081
28.28
4.93
1.00
23.74

1811
OD2
ASP
A
441
34.135
27.02
3.409
1.00
23.76

1812
C
ASP
A
441
31.479
30.26
5.888
1.00
17.16

1813
O
ASP
A
441
31.543
31.45
5.56
1.00
16.05

1814
N
LEU
A
442
30.351
29.69
6.299
1.00
15.92

1815
CA
LEU
A
442
29.1
30.44
6.373
1.00
15.51

1816
CB
LEU
A
442
27.921
29.5
6.648
1.00
14.97

1817
CG
LEU
A
442
27.461
28.65
5.457
1.00
16.25

1818
CD1
LEU
A
442
26.459
27.62
5.923
1.00
15.43

1819
CD2
LEU
A
442
26.835
29.54
4.389
1.00
16.30

1820
C
LEU
A
442
29.149
31.53
7.441
1.00
16.51

1821
O
LEU
A
442
28.64
32.62
7.243
1.00
15.91

1822
N
ARG
A
443
29.758
31.21
8.578
1.00
17.51

1823
CA
ARG
A
443
29.859
32.19
9.656
1.00
19.49

1824
CB
ARG
A
443
30.545
31.56
10.868
1.00
20.19

1825
CG
ARG
A
443
30.518
32.44
12.104
1.00
24.32

1826
CD
ARG
A
443
30.919
31.66
13.334
1.00
27.77

1827
NE
ARG
A
443
29.938
30.63
13.68
1.00
30.42

1828
CZ
ARG
A
443
29.983
29.92
14.799
1.00
32.49

1829
NH1
ARG
A
443
30.963
30.12
15.669
1.00
33.93

1830
NH2
ARG
A
443
29.052
29.01
15.058
1.00
32.62

1831
C
ARG
A
443
30.649
33.4
9.171
1.00
19.24

1832
O
ARG
A
443
30.288
34.54
9.451
1.00
20.11

1833
N
GLN
A
444
31.729
33.15
8.441
1.00
20.35

1834
CA
GLN
A
444
32.555
34.23
7.906
1.00
21.41

1835
CB
GLN
A
444
33.831
33.66
7.278
1.00
23.62

1836
CG
GLN
A
444
34.618
34.65
6.433
1.00
28.57

1837
CD
GLN
A
444
35.508
35.57
7.25
1.00
33.29

1838
OE1
GLN
A
444
35.105
36.09
8.293
1.00
36.07

1839
NE2
GLN
A
444
36.728
35.79
6.768
1.00
36.08

1840
C
GLN
A
444
31.761
34.99
6.852
1.00
20.82

1841
O
GLN
A
444
31.776
36.22
6.815
1.00
19.43

1842
N
LEU
A
445
31.062
34.25
5.997
1.00
19.72

1843
CA
LEU
A
445
30.255
34.85
4.943
1.00
18.86

1844
CB
LEU
A
445
29.577
33.75
4.112
1.00
18.95

1845
CG
LEU
A
445
28.856
34.16
2.826
1.00
20.08

1846
CD1
LEU
A
445
29.888
34.62
1.793
1.00
20.86

1847
CD2
LEU
A
445
28.06
32.97
2.275
1.00
21.90

1848
C
LEU
A
445
29.19
35.78
5.53
1.00
18.74

1849
O
LEU
A
445
28.909
36.84
4.963
1.00
17.29

1850
N
VAL
A
446
28.596
35.39
6.658
1.00
17.24

1851
CA
VAL
A
446
27.565
36.23
7.287
1.00
17.47

1852
CB
VAL
A
446
26.781
35.45
8.367
1.00
17.76

1853
CG1
VAL
A
446
25.852
36.4
9.126
1.00
18.67

1854
CG2
VAL
A
446
25.955
34.34
7.711
1.00
1452

1855
C
VAL
A
446
28.171
37.48
7.927
1.00
18.46

1856
O
VAL
A
446
27.612
38.57
7.832
1.00
18.68

1857
N
THR
A
447
29.311
37.3
8.584
1.00
18.45

1858
CA
THR
A
447
29.984
38.42
9.232
1.00
19.82

1859
CB
THR
A
447
31.313
37.97
9.872
1.00
20.76

1860
OG1
THR
A
447
31.048
36.96
10.85
1.00
22.73

1861
CG2
THR
A
447
32.008
39.14
10.542
1.00
23.28

1862
C
THR
A
447
30.272
39.5
8.197
1.00
20.08

1863
O
THR
A
447
30.04
40.69
8.434
1.00
20.49

1864
N
GLU
A
448
30.777
39.07
7.044
1.00
18.53

1865
CA
GLU
A
448
31.104
39.98
5.963
1.00
19.18

1866
CB
GLU
A
448
31.901
39.23
4.889
1.00
19.51

1867
CG
GLU
A
448
33.064
38.45
5.485
1.00
23.78

1868
CD
GLU
A
448
33.905
37.72
4.454
1.00
25.56

1869
OE1
GLU
A
448
33.331
37.13
3.518
1.00
27.66

1870
OE2
GLU
A
448
35.147
37.73
4.592
1.00
27.05

1871
C
GLU
A
448
29.85
40.61
5.358
1.00
17.55

1872
O
GLU
A
448
29.86
41.77
4.961
1.00
18.18

1873
N
HIS
A
449
28.771
39.84
5.283
1.00
16.47

1874
CA
HIS
A
449
27.526
40.35
4.729
1.00
15.35

1875
CB
HIS
A
449
26.509
39.22
4.559
1.00
13.45

1876
CG
HIS
A
449
25.167
39.67
4.061
1.00
13.44

1877
CD2
HIS
A
449
24
39.87
4.715
1.00
14.46

1878
ND1
HIS
A
449
24.914
39.94
2.734
1.00
14.54

1879
CE1
HIS
A
449
23.65
40.3
2.593
1.00
14.39

1880
NE2
HIS
A
449
23.072
40.26
3.78
1.00
14.22

1881
C
HIS
A
449
26.949
41.44
5.633
1.00
15.34

1882
O
HIS
A
449
26.508
42.48
5.145
1.00
16.88

1883
N
ALA
A
450
26.953
41.22
6.942
1.00
16.12

1884
CA
ALA
A
450
26.422
42.2
7.883
1.00
17.96

1885
CB
ALA
A
450
26.507
41.67
9.31
1.00
17.75

1886
C
ALA
A
450
27.191
43.52
7.776
1.00
19.46

1887
O
ALA
A
450
26.623
44.6
7.958
1.00
18.94

1888
N
GLN
A
451
28.482
43.43
7.481
1.00
21.32

1889
CA
GLN
A
451
29.31
44.63
7.348
1.00
22.42

1890
CB
GLN
A
451
30.779
44.25
7.151
1.00
26.37

1891
CG
GLN
A
451
31.721
45.44
7.069
1.00
31.72

1892
CD
GLN
A
451
33.179
45.03
6.974
1.00
34.48

1893
OE1
GLN
A
451
33.653
44.21
7.757
1.00
37.93

1894
NE2
GLN
A
451
33.897
45.6
6.016
1.00
35.81

1895
C
GLN
A
451
28.831
45.45
6.161
1.00
21.76

1896
O
GLN
A
451
28.707
46.67
6.247
1.00
20.34

1897
N
LEU
A
452
28.556
44.77
5.05
1.00
19.43

1898
CA
LEU
A
452
28.086
45.46
3.855
1.00
20.58

1899
CB
LEU
A
452
28.063
44.5
2.662
1.00
21.26

1900
CG
LEU
A
452
27.566
45.09
1.338
1.00
23.72

1901
GD1
LEU
A
452
28.481
46.24
0.906
1.00
23.27

1902
GD2
LEU
A
452
27.531
44
0.277
1.00
23.43

1903
C
LEU
A
452
26.688
46.01
4.107
1.00
19.34

1904
O
LEU
A
452
26.369
47.12
3.676
1.00
20.88

1905
N
VAL
A
453
25.857
45.25
4.811
1.00
19.86

1906
CA
VAL
A
453
24.501
45.69
5.125
1.00
19.89

1907
CB
VAL
A
453
23.719
44.61
5.923
1.00
21.23

1908
CG1
VAL
A
453
22.35
45.14
6.342
1.00
22.52

1909
CG2
VAL
A
453
23.538
43.36
5.063
1.00
20.41

1910
C
VAL
A
453
24.557
46.99
5.938
1.00
21.15

1911
O
VAL
A
453
23.745
47.89
5.733
1.00
20.95

1912
N
GLN
A
454
25.522
47.08
6.847
1.00
21.46

1913
CA
GLN
A
454
25.669
48.28
7.667
1.00
23.89

1914
CB
GLN
A
454
26.729
48.05
8.749
1.00
27.62

1915
CG
GLN
A
454
26.848
49.2
9.754
1.00
32.28

1916
CD
GLN
A
454
25.615
49.35
10.635
1.00
35.43

1917
OE1
GLN
A
454
25.592
50.18
11.546
1.00
38.17

1918
NE2
GLN
A
454
24.586
48.55
10.371
1.00
37.92

1919
C
GLN
A
454
26.066
49.47
6.789
1.00
24.56

1920
O
GLN
A
454
25.59
50.58
6.993
1.00
22.97

1921
N
ILE
A
455
26.938
49.22
5.817
1.00
23.13

1922
CA
ILE
A
455
27.383
50.27
4.915
1.00
24.75

1923
CB
ILE
A
455
28.474
49.75
3.948
1.00
24.82

1924
CG2
ILE
A
455
28.746
50.76
2.846
1.00
24.01

1925
CG1
ILE
A
455
29.755
49.45
4.738
1.00
25.40

1926
CD1
ILE
A
455
30.846
48.78
3.935
1.00
25.53

1927
C
ILE
A
455
26.203
50.79
4.109
1.00
25.90

1928
O
ILE
A
455
26
52
3.969
1.00
26.44

1929
N
ILE
A
456
25.41
49.86
3.578
1.00
26.77

1930
CA
ILE
A
456
24.232
50.2
2.798
1.00
29.88

1931
CB
ILE
A
456
23.559
48.93
2.21
1.00
30.75

1932
CG2
ILE
A
456
22.188
49.27
1.69
1.00
33.39

1933
CG1
ILE
A
456
24.366
48.35
1.059
1.00
31.69

1934
OD1
ILE
A
456
23.79
47.03
0.547
1.00
34.09

1935
C
ILE
A
456
23.244
50.94
3.689
1.00
30.49

1936
O
ILE
A
456
22.611
51.92
3.278
1.00
30.43

1937
N
LYS
A
457
23.101
50.5
4.922
1.00
32.72

1938
CA
LYS
A
457
22.172
51.15
5.818
1.00
36.04

1939
CB
LYS
A
457
22.139
50.37
7.131
1.00
37.66

1940
CG
LYS
A
457
21.215
50.95
8.145
1.00
40.69

1941
CD
LYS
A
457
20.92
49.91
9.19
1.00
41.72

1942
CE
LYS
A
457
19.917
50.43
10.191
1.00
44.25

1943
NZ
LYS
A
457
20.495
51.43
11.136
1.00
45.65

1944
C
LYS
A
457
22.479
52.63
6.094
1.00
36.68

1945
O
LYS
A
457
21.564
53.45
6.176
1.00
36.26

1946
N
LYS
A
458
23.756
52.97
6.213
1.00
37.99

1947
CA
LYS
A
458
24.132
54.35
6.501
1.00
39.24

1948
CB
LYS
A
458
25.327
54.38
7.465
1.00
41.14

1949
CG
LYS
A
458
26.689
54.41
6.785
1.00
43.28

1950
GD
LYS
A
458
27.822
54.42
7.806
1.00
44.36

1951
CE
LYS
A
458
27.936
53.09
8.516
1.00
45.26

1952
NZ
LYS
A
458
28.212
51.99
7.55
1.00
44.67

1953
C
LYS
A
458
24.459
55.18
5.258
1.00
39.55

1954
O
LYS
A
458
24.528
56.41
5.321
1.00
39.79

1955
N
THR
A
459
24.65
54.5
4.132
1.00
39.02

1956
CA
THR
A
459
24.988
55.16
2.88
1.00
39.78

1957
CB
THR
A
459
26.164
54.43
2.182
1.00
40.83

1958
OG1
THR
A
459
27.404
54.92
2.715
1.00
41.96

1959
CG2
THR
A
459
26.136
54.65
0.68
1.00
42.44

1960
C
THR
A
459
23.823
55.29
1.901
1.00
39.33

1961
O
THR
A
459
23.734
56.27
1.16
1.00
39.15

1962
N
GLU
A
460
22.934
54.31
1.892
1.00
38.93

1963
CA
GLU
A
460
21.792
54.33
0.989
1.00
39.36

1964
CB
GLU
A
460
21.621
52.97
0.312
1.00
37.13

1965
CG
GLU
A
460
22.799
52.51
−0.549
1.00
33.20

1966
CD
GLU
A
460
22.988
53.33
−1.812
1.00
31.38

1967
OE1
GLU
A
460
21.988
53.86
−2.345
1.00
31.23

1968
OE2
GLU
A
460
24.137
53.44
−2.288
1.00
27.05

1969
C
GLU
A
460
20.514
54.69
1.742
1.00
41.61

1970
O
GLU
A
460
19.856
53.82
2.308
1.00
41.95

1971
N
SER
A
461
20.167
55.97
1.755
1.00
44.12

1972
CA
SER
A
461
18.958
56.41
2.439
1.00
46.91

1973
CB
SER
A
461
19.07
57.89
2.821
1.00
47.79

1974
OG
SER
A
461
20.075
58.09
3.805
1.00
49.02

1975
C
SER
A
461
17.769
56.2
1.516
1.00
48.12

1976
O
SER
A
461
16.613
56.29
1.928
1.00
48.49

1977
N
ASP
A
462
18.077
55.91
0.257
1.00
49.25

1978
CA
ASP
A
462
17.068
55.65
−0.758
1.00
50.01

1979
CB
ASP
A
462
17.751
55.26
−2.067
1.00
51.19

1980
CG
ASP
A
462
19.027
54.46
−1.839
1.00
51.21

1981
OD1
ASP
A
462
19.959
55.01
−1.215
1.00
52.21

1982
OD2
ASP
A
462
19.103
53.3
−2.279
1.00
52.20

1983
C
ASP
A
462
16.161
54.53
−0.285
1.00
49.54

1984
O
ASP
A
462
14.948
54.57
−0.482
1.00
50.36

1985
N
ALA
A
463
16.769
53.54
0.346
1.00
49.32

1986
CA
ALA
A
463
16.044
52.39
0.864
1.00
47.69

1987
CB
ALA
A
463
16.147
51.24
−0.105
1.00
48.66

1988
C
ALA
A
463
16.65
52.01
2.209
1.00
46.49

1989
O
ALA
A
463
17.867
52.01
2.365
1.00
47.87

1990
N
ALA
A
464
15.797
51.69
3.177
1.00
43.89

1991
CA
ALA
A
464
16.251
51.34
4.514
1.00
41.22

1992
CB
ALA
A
464
15.312
51.94
5.553
1.00
41.01

1993
C
ALA
A
464
16.349
49.83
4.714
1.00
39.82

1994
O
ALA
A
464
17.077
49.14
3.987
1.00
41.52

1995
N
LEU
A
465
15.628
49.33
5.715
1.00
36.01

1996
CA
LEU
A
465
15.588
47.9
6.058
1.00
32.30

1997
CB
LEU
A
465
16.754
47.51
6.977
1.00
33.09

1998
CG
LEU
A
465
18.085
47.02
6.399
1.00
33.05

1999
CD1
LEU
A
465
18.95
46.51
7.545
1.00
32.55

2000
CD2
LEU
A
465
17.854
45.9
5.398
1.00
31.55

2001
C
LEU
A
465
14.284
47.56
6.771
1.00
29.76

2002
O
LEU
A
465
13.78
48.34
7.59
1.00
26.72

2003
N
HIS
A
466
13.749
46.38
6.458
1.00
26.87

2004
CA
HIS
A
466
12.511
45.9
7.057
1.00
25.80

2005
CB
HIS
A
466
12.115
44.56
6.418
1.00
24.73

2006
CG
HIS
A
466
10.849
43.98
6.964
1.00
25.28

2007
CD2
HIS
A
466
10.576
43.4
8.157
1.00
24.58

2008
ND1
HIS
A
466
9.678
43.92
6.237
1.00
26.52

2009
CE1
HIS
A
466
8.739
43.34
6.959
1.00
25.66

2010
NE2
HIS
A
466
9.259
43.01
8.13
1.00
26.42

2011
C
HIS
A
466
12.716
45.72
8.563
1.00
25.90

2012
O
HIS
A
466
13.796
45.33
9.009
1.00
25.20

2013
N
PRO
A
467
11.674
46
9.364
1.00
25.60

2014
CD
PRO
A
467
10.372
46.55
8.935
1.00
26.08

2015
CA
PRO
A
467
11.724
45.87
10.823
1.00
25.42

2016
CE
PRO
A
467
10.262
46.04
11.223
1.00
25.91

2017
CG
PRO
A
467
9.78
47.04
10.238
1.00
27.38

2018
C
PRO
A
467
12.317
44.56
11.335
1.00
25.07

2019
O
PRO
A
467
13.16
44.56
12.233
1.00
25.29

2020
N
LEU
A
468
11.873
43.44
10.774
1.00
23.71

2021
CA
LEU
A
468
12.378
42.15
11.215
1.00
22.76

2022
CB
LEU
A
468
11.611
41
10.538
1.00
22.31

2023
CG
LEU
A
468
12.092
39.58
10.878
1.00
22.34

2024
CD1
LEU
A
468
11.953
39.32
12.379
1.00
23.76

2025
CD2
LEU
A
468
11.277
38.57
10.09
1.00
22.76

2026
C
LEU
A
468
13.866
42
10.927
1.00
22.18

2027
O
LEU
A
468
14.617
41.49
11.756
1.00
21.97

2028
N
LEU
A
469
14.296
42.44
9.752
1.00
21.66

2029
CA
LEU
A
469
15.704
42.34
9.394
1.00
21.60

2030
CE
LEU
A
469
15.885
42.62
7.899
1.00
20.70

2031
CG
LEU
A
469
14.968
41.76
7.024
1.00
19.18

2032
CD1
LEU
A
469
15.329
41.95
5.56
1.00
20.00

2033
CD2
LEU
A
469
15.104
40.29
7.424
1.00
16.85

2034
C
LEU
A
469
16.534
43.3
10.231
1.00
23.25

2035
O
LEU
A
469
17.671
43.01
10.613
1.00
21.71

2036
N
GLN
A
470
15.953
44.46
10.531
1.00
23.59

2037
CA
GLN
A
470
16.649
45.44
11.332
1.00
26.43

2038
CB
GLN
A
470
15.819
46.72
11.436
1.00
28.61

2039
CG
GLN
A
470
16.52
47.84
12.192
1.00
34.25

2040
CD
GLN
A
470
17.805
48.3
11.52
1.00
36.90

2041
OE1
GLN
A
470
18.567
49.08
12.092
1.00
40.50

2042
NE2
GLN
A
470
18.048
47.82
10.303
1.00
38.17

2043
C
GLN
A
470
16.95
44.9
12.727
1.00
25.75

2044
O
GLN
A
470
18.057
45.07
13.229
1.00
27.57

2045
N
GLU
A
471
15.986
44.22
13.354
1.00
25.39

2046
CA
GLU
A
471
16.239
43.7
14.693
1.00
26.81

2047
CB
GLU
A
471
14.929
43.29
15.397
1.00
28.93

2048
CG
GLU
A
471
14.136
42.15
14.784
1.00
30.21

2049
CD
GLU
A
471
12.837
41.88
15.551
1.00
32.16

2050
QE1
GLU
A
471
11.987
42.79
15.629
1.00
32.22

2051
0E2
GLU
A
471
12.665
40.76
16.077
1.00
30.73

2052
C
GLU
A
471
17.24
42.55
14.681
1.00
25.84

2053
O
GLU
A
471
17.978
42.34
15.648
1.00
25.91

2054
N
ILE
A
472
17.287
41.79
13.586
1.00
23.23

2055
CA
ILE
A
472
18.238
40.7
13.498
1.00
22.62

2056
CB
ILE
A
472
17.941
39.78
12.282
1.00
23.65

2057
CG2
ILE
A
472
19.106
38.81
12.049
1.00
21.96

2058
CG1
ILE
A
472
16.642
39.01
12.531
1.00
22.25

2059
CD1
ILE
A
472
16.172
38.18
11.345
1.00
24.20

2060
C
ILE
A
472
19.656
41.27
13.392
1.00
23.04

2061
O
ILE
A
472
20.567
40.79
14.061
1.00
20.73

2062
N
TYR
A
473
19.836
42.3
12.57
1.00
23.82

2063
CA
TYR
A
473
21.159
42.9
12.394
1.00
25.85

2064
CB
TYR
A
473
21.233
43.63
11.057
1.00
24.50

2065
CG
TYR
A
473
21.41
42.69
9.887
1.00
22.75

2066
CD1
TYR
A
473
22.574
41.94
9.749
1.00
23.07

2067
CE1
TYR
A
473
22.723
41.03
8.695
1.00
22.58

2068
CD2
TYR
A
473
20.401
42.53
8.945
1.00
23.44

2069
CE2
TYR
A
473
20.539
41.63
7.896
1.00
20.95

2070
CZ
TYR
A
473
21.698
40.89
7.777
1.00
22.05

2071
OH
TYR
A
473
21.822
39.99
6.74
1.00
21.31

2072
C
TYR
A
473
21.608
43.82
13.519
1.00
27.80

2073
O
TYR
A
473
22.805
44.05
13.69
1.00
28.04

2074
N
AkO
A
474
20.661
44.36
14.282
1.00
29.91

2075
CA
ARG
A
474
21.006
45.25
15.391
1.00
33.29

2076
CB
ARG
A
474
19.737
45.78
16.068
1.00
35.76

2077
CG
ARG
A
474
19.987
46.55
17.366
1.00
38.99

2078
CD
ARG
A
474
18.675
47.02
17.984
1.00
42.46

2079
NE
ARG
A
474
18.862
47.7
19.265
1.00
44.44

2080
CZ
ARG
A
474
17.879
48.28
19.953
1.00
46.85

2081
NH1
ARG
A
474
16.637
48.26
19.485
1.00
47.83

2082
NH2
ARG
A
474
18.134
48.87
21.111
1.00
47.38

2083
C
ARG
A
474
21.859
44.51
16.42
1.00
34.75

2084
O
ARG
A
474
21.409
43.53
17.025
1.00
34.47

2085
N
ASP
A
475
23.094
44.97
16.604
1.00
36.62

2086
CA
ASP
A
475
24.019
44.37
17.563
1.00
38.83

2087
CB
ASP
A
475
23.447
44.45
18.982
1.00
39.46

2088
CG
ASP
A
475
23.228
45.88
19.434
1.00
40.61

2089
OD1
ASP
A
475
24.135
46.72
19.217
1.00
40.51

2090
OD2
ASP
A
475
22.156
46.17
20.014
1.00
40.94

2091
C
ASP
A
475
24.396
42.92
17.274
1.00
39.96

2092
O
ASP
A
475
24.768
42.18
18.187
1.00
39.85

2093
N
MET
A
476
24.303
42.5
16.015
1.00
41.66

2094
CA
MET
A
476
24.664
41.13
15.66
1.00
43.69

2095
CB
MET
A
476
24.33
40.85
14.196
1.00
43.01

2096
CG
MET
A
476
24.632
39.42
13.777
1.00
43.53

2097
SD
MET
A
476
24.318
39.13
12.035
1.00
45.18

2098
CE
MET
A
476
22.532
38.88
12.057
1.00
44.23

2099
C
MET
A
476
26.163
40.97
15.882
1.00
45.56

2100
O
MET
A
476
26.603
40.18
16.718
1.00
46.26

2101
N
TYR
A
477
26.942
41.73
15.12
1.00
46.99

2102
CA
TYR
A
477
28.394
41.7
15.225
1.00
48.84

2103
CB
TYR
A
477
29.023
41.13
13.949
1.00
48.71

2104
CG
TYR
A
477
28.735
39.65
13.725
1.00
48.95

2105
CD1
TYR
A
477
27.925
39.23
12.67
1.00
49.23

2106
CE1
TYR
A
477
27.653
37.88
12.466
1.00
49.07

2107
CD2
TYR
A
477
29.268
38.68
14.574
1.00
49.57

2108
CE2
TYR
A
477
29.003
37.33
14.381
1.00
49.37

2109
GZ
TYR
A
477
28.196
36.93
13.327
1.00
49.98

2110
OH
TYR
A
477
27.937
35.59
13.14
1.00
49.98

2111
C
TYR
A
477
28.888
43.13
15.459
1.00
49.62

2112
O
TYR
A
477
29.046
43.86
14.465
1.00
50.21

2113
OT
TYR
A
477
29.08
43.5
16.638
1.00
50.66

2114
CB
GLU
B
685
18.563
43.31
21.966
1.00
63.65

2115
CG
GLU
B
685
18.355
43.18
23.466
1.00
63.87

2116
CD
GLU
B
685
18.5
41.75
23.944
1.00
64.23

2117
OE1
GLU
B
685
17.602
40.93
23.645
1.00
64.28

2118
OE2
GLU
B
685
19.509
41.44
24.611
1.00
64.53

2119
C
GLU
B
685
16.485
44.44
21.146
1.00
61.94

2120
O
GLU
B
685
15.976
44.7
20.055
1.00
62.27

2121
N
GLU
B
685
18.315
45.76
22.219
1.00
62.90

2122
CA
GLU
B
685
17.989
44.59
21.355
1.00
62.73

2123
N
ARG
B
686
15.783
44.01
22.191
1.00
60.58

2124
CA
ARG
B
686
14.335
43.82
22.134
1.00
59.13

2125
CB
ARG
B
686
13.674
45.08
21.56
1.00
60.07

2126
CG
ARG
B
686
12.151
45.06
21.524
1.00
61.27

2127
CD
ARG
B
686
11.543
45.61
22.805
1.00
62.16

2128
NE
ARG
B
686
10.168
46.05
22.594
1.00
63.43

2129
CZ
ARG
B
686
9.147
45.24
22.329
1.00
64.44

2130
NH1
ARG
B
686
9.339
43.93
22.247
1.00
64.89

2131
NH2
ARG
B
686
7.936
45.75
22.128
1.00
65.34

2132
C
ARG
B
686
13.932
42.6
21.299
1.00
57.39

2133
O
ARG
B
686
13.69
41.52
21.841
1.00
58.48

2134
N
HIS
B
687
13.867
42.78
19.982
1.00
54.71

2135
CA
HIS
B
687
13.479
41.72
19.052
1.00
51.16

2136
CB
HIS
B
687
14.316
40.46
19.28
1.00
51.72

2137
CG
HIS
B
687
15.776
40.64
19.004
1.00
51.47

2138
CD2
HIS
B
687
16.561
40.16
18.01
1.00
51.61

2139
ND1
HIS
B
687
16.596
41.41
19.802
1.00
52.04

2140
CE1
HIS
B
687
17.822
41.39
19.311
1.00
51.83

2141
NE2
HIS
B
687
17.828
40.64
18.225
1.00
51.34

2142
C
HIS
B
687
11.998
41.39
19.21
1.00
48.80

2143
O
HIS
B
687
11.628
40.24
19.412
1.00
48.44

2144
N
ALA
B
688
11.157
42.41
19.108
1.00
45.79

2145
CA
ALA
B
688
9.714
42.25
19.251
1.00
43.75

2146
CB
ALA
B
688
9.027
43.61
19.108
1.00
43.70

2147
C
ALA
B
688
9.106
41.26
18.265
1.00
41.94

2148
O
ALA
B
688
8.488
40.27
18.669
1.00
40.94

2149
N
ILE
B
689
9.282
41.52
16.973
1.00
40.75

2150
CA
ILE
B
689
8.728
40.65
15.939
1.00
39.42

2151
CB
ILE
B
689
9.093
41.17
14.532
1.00
39.12

2152
G02
ILE
B
689
8.624
40.18
13.468
1.00
38.63

2153
CG1
ILE
B
689
8.444
42.54
14.312
1.00
38.90

2154
CD1
ILE
B
689
8.728
43.15
12.959
1.00
39.20

2155
C
ILE
B
689
9.18
39.2
16.077
1.00
38.83

2156
O
ILE
B
689
8.36
38.28
16.039
1.00
37.60

2157
N
LEU
B
690
10.482
39
16.24
1.00
38.40

2158
CA
LEU
B
690
11.027
37.66
16.389
1.00
38.63

2159
CB
LEU
B
690
12.54
37.74
16.596
1.00
39.36

2160
CG
LEU
B
690
13.378
36.57
16.066
1.00
40.30

2161
CD1
LEU
B
690
14.853
36.95
16.107
1.00
39.81

2162
CD2
LEU
B
690
13.111
35.32
16.884
1.00
41.50

2163
C
LEU
B
690
10.352
36.99
17.584
1.00
39.78

2164
O
LEU
B
690
9.892
35.85
17.491
1.00
38.83

2165
N
HIS
B
691
10.287
37.7
18.707
1.00
40.27

2166
CA
HIS
B
691
9.64
37.17
19.902
1.00
41.72

2167
CB
HIS
B
691
9.659
38.2
21.029
1.00
43.49

2168
CG
HIS
B
691
10.89
38.15
21.877
1.00
45.34

2169
CD2
HIS
B
691
11.897
39.04
22.045
1.00
46.24

2170
ND1
HIS
B
691
11.185
37.08
22.695
1.00
46.60

2171
CE1
HIS
B
691
12.319
37.31
23.33
1.00
46.83

2172
NE2
HIS
B
691
12.772
38.49
22.954
1.00
47.22

2173
C
HIS
B
691
8.198
36.79
19.584
1.00
41.36

2174
O
HIS
B
691
7.732
35.71
19.945
1.00
41.77

2175
N
ARG
B
692
7.497
37.69
18.904
1.00
40.51

2176
CA
ARO
B
692
6.108
37.46
18.531
1.00
40.58

2177
CB
ARG
B
692
5.585
38.62
17.68
1.00
41.97

2178
CG
ARG
B
692
4.103
38.54
17.334
1.00
44.31

2179
CD
ARG
B
692
3.748
39.58
16.287
1.00
46.39

2180
NE
AkG
B
692
4.433
39.31
15.024
1.00
48.87

2181
CZ
ARG
B
692
4.503
40.17
14.009
1.00
49.52

2182
NH1
ARG
B
692
3.928
41.36
14.099
1.00
50.67

2183
NH2
ARG
B
692
5.15
39.83
12.901
1.00
49.63

2184
C
ARG
B
692
5.99
36.15
17.748
1.00
39.77

2185
O
ARG
B
692
5.238
35.25
18.134
1.00
38.70

2186
N
LEU
B
693
6.739
36.05
16.652
1.00
38.99

2187
CA
LEU
B
693
6.718
34.85
15.816
1.00
39.44

2188
CB
LEU
B
693
7.804
34.92
14.735
1.00
38.36

2189
CG
LEU
B
693
7.65
35.94
13.602
1.00
38.71

2190
CD1
LEU
B
693
8.863
35.86
12.69
1.00
37.17

2191
CD2
LEU
B
693
6.38
35.65
12.815
1.00
37.74

2192
C
LEU
B
693
6.924
33.59
16.642
1.00
40.12

2193
O
LEU
B
693
6.275
32.57
16.412
1.00
40.20

2194
N
LEU
B
694
7.834
33.66
17.606
1.00
41.30

2195
CA
LEU
B
694
8.116
32.51
18.455
1.00
43.03

2196
CB
LEU
B
694
9.4
32.75
19.249
1.00
41.27

2197
CG
LEU
B
694
10.684
32.76
18.413
1.00
40.09

2198
CD1
LEU
B
694
11.845
33.25
19.251
1.00
39.04

2199
CD2
LEU
B
694
10.953
31.36
17.879
1.00
39.24

2200
C
LEU
B
694
6.967
32.19
19.407
1.00
45.64

2201
O
LEU
B
694
6.867
31.07
19.907
1.00
44.78

2202
N
GLN
B
695
6.098
33.17
19.645
1.00
49.29

2203
CA
GLN
B
695
4.964
32.98
20.55
1.00
53.51

2204
CB
GLN
B
695
4.348
34.33
20.927
1.00
53.94

2205
CG
GLN
B
695
5.333
35.37
21.451
1.00
54.96

2206
CD
GLN
B
695
6.079
34.93
22.698
1.00
55.61

2207
OE1
GLN
B
695
6.874
35.68
23.258
1.00
55.52

2208
NE2
GLN
B
695
5.828
33.7
23.138
1.00
55.62

2209
C
GLN
B
695
3.877
32.09
19.953
1.00
55.94

2210
O
GLN
B
695
3.046
31.55
20.681
1.00
55.76

2211
N
GLU
B
696
3.88
31.96
18.629
1.00
58.97

2212
CA
GLU
B
696
2.889
31.14
17.938
1.00
62.61

2213
CB
GLU
B
696
1.479
31.66
18.24
1.00
63.02

2214
CG
GLU
B
696
1.349
33.18
18.306
1.00
63.82

2215
CD
GLU
B
696
1.774
33.87
17.026
1.00
64.13

2216
OE1
GLU
B
696
1.142
33.63
15.977
1.00
64.51

2217
OE2
GLU
B
696
2.743
34.66
17.072
1.00
64.16

2218
C
GLU
B
696
3.104
31.1
16.429
1.00
64.98

2219
O
GLU
B
696
2.736
30.12
15.772
1.00
65.58

2220
N
GLY
B
697
3.699
32.15
15.883
1.00
67.35

2221
CA
GLY
B
697
3.946
32.2
14.454
1.00
70.03

2222
C
GLY
B
697
3.53
33.52
13.838
1.00
71.80

2223
O
GLY
B
697
3.13
34.45
14.543
1.00
71.76

2224
O
HOH
S
1
23.026
22.4
−2.192
1.00
19.60

2225
O
HOH
S
2
16.83
36.19
0.675
1.00
18.07

2226
O
HOH
S
3
22.154
35.44
11.146
1.00
15.63

2227
O
HOH
S
4
24.973
20.25
−2.261
1.00
20.14

2228
O
HOH
S
5
22.161
29.6
15.788
1.00
19.70

2229
O
HOH
S
6
24.965
31.5
−0.66
1.00
16.40

2230
O
HOH
S
7
10.844
33.69
−3.369
1.00
17.23

2231
O
HOH
S
8
22.447
38.7
−17.98
1.00
31.92

2232
O
HOH
S
9
17.526
31.03
1.265
1.00
14.10

2233
O
HOH
S
10
29.027
37.84
2.226
1.00
16.59

2234
O
HOH
S
11
16.149
33.62
0.874
1.00
17.71

2235
O
HOH
S
12
21.554
23.97
−0.428
1.00
13.97

2236
O
HOH
S
13
24.572
41.48
−5.871
1.00
19.10

2237
O
HOH
S
14
34.349
22.18
2.662
1.00
23.28

2238
O
HOH
S
15
23.974
19.69
−6.03
1.00
21.97

2239
O
HOH
S
16
12.346
31.08
−5.777
1.00
18.26

2240
O
HOH
S
17
17.302
24.21
0.483
1.00
21.48

2241
O
HOH
S
18
12.779
35.67
−4.261
1.00
15.87

2242
O
HOH
S
19
32.946
42.65
9.74
1.00
47.61

2243
O
HOH
S
20
6.647
45.31
0.256
1.00
32.40

2244
O
HOH
S
21
11.636
46.33
3.1
1.00
47.12

2245
O
HOH
S
22
15.387
32.46
−1.723
1.00
24.92

2246
O
HOH
S
23
15.179
49.11
−1.349
1.00
26.79

2247
O
HOH
S
24
17.323
27.72
27.462
1.00
23.87

2248
O
HOH
S
25
32.126
32.89
−0.975
1.00
24.24

2249
O
HOH
S
26
17.22
13.39
7.072
1.00
30.98

2250
O
HOH
S
27
17.61
52.48
−12.57
1.00
30.41

2251
O
HOH
S
28
11.598
28.45
0.826
1.00
27.74

2252
O
HOH
S
29
29.348
58.2
3.202
1.00
24.47

2253
O
HOH
S
30
20.33
34.13
24.733
1.00
27.25

2254
O
HOH
S
31
11.314
30.72
−3.163
1.00
29.15

2255
O
HOH
S
32
14.534
17.66
−8.919
1.00
23.07

2256
O
HOH
S
33
12.594
30.55
30.559
1.00
24.86

2257
O
HOH
S
34
4.997
18.18
3.778
1.00
28.69

2258
O
HOH
S
35
14.93
26.08
0.846
1.00
31.48

2259
O
HOH
S
36
26.37
38.41
−9.188
1.00
23.21

2260
O
HOH
S
37
1.85
51.46
−7.183
1.00
42.96

2261
O
HOH
S
38
30.499
11.23
5.931
1.00
32.46

2262
O
HOH
S
39
11.29
49.8
6.081
1.00
48.93

2263
O
HOH
S
40
20.535
16.89
−4.929
1.00
32.28

2264
O
HOH
S
41
24.859
35.08
−15.49
1.00
21.88

2265
O
HOH
S
42
7.686
40.68
3.298
1.00
37.33

2266
O
HOH
S
43
27.519
46.28
−18.33
1.00
37.96

2267
O
HOH
S
44
22.661
13.79
−4.577
1.00
49.60

2268
O
HOH
S
45
7.412
32.25
11.943
1.00
23.05

2269
O
HOH
S
46
31.273
40.98
1.303
1.00
31.68

2270
O
HOH
S
47
33.257
32.33
3.506
1.00
19.13

2271
O
HOH
S
48
6.534
16.95
5.915
1.00
23.85

2272
O
HOH
S
49
17.618
50.65
7.877
1.00
28.11

2273
O
HOH
S
50
20.823
9.387
10.717
1.00
28.29

2274
O
HOH
S
51
13.363
37.04
29.626
1.00
23.94

2275
O
HOH
S
52
9.174
18.86
−1.964
1.00
33.23

2276
O
HOH
S
53
23.557
48.69
−14.77
1.00
55.81

2277
O
HOH
S
54
33.983
34.75
2.856
1.00
26.86

2278
O
HOH
S
55
29.833
11
8.326
1.00
28.51

2279
O
HOH
S
57
11.766
42.24
23.635
1.00
42.57

2280
O
HOH
S
58
14.76
33.63
−4.189
1.00
32.75

2281
O
HOH
S
59
12.5
34.34
29.874
1.00
22.65

2282
O
HOH
S
60
28.126
41.87
−15.42
1.00
31.74

2283
O
HOH
S
61
26.365
40.53
−7.535
1.00
22.73

2284
O
HOH
S
62
22.279
46.65
−15.85
1.00
50.83

2285
O
HOH
S
63
7.178
15.42
0.05
1.00
44.46

2286
O
HOH
S
64
3.624
30.59
−0.214
1.00
36.39

2287
O
HOH
S
65
6.139
27.86
3.768
1.00
52.56

2288
O
HOH
S
66
31.097
55.49
8.217
1.00
30.35

2289
O
HOH
S
67
18.605
58.14
−1.051
1.00
47.14

2290
O
HOH
S
68
8.343
23.64
26.996
1.00
32.72

2291
O
HOH
S
69
19.685
57.59
−3.396
1.00
43.61

2292
O
HOH
S
70
20.943
28.28
33.357
1.00
40.59

2293
O
HOH
S
71
21.649
36.71
27.743
1.00
35.00

2294
O
HOH
S
72
31.539
42.79
3.263
1.00
30.88

2295
O
HOH
S
73
13.289
50.24
2.509
1.00
38.75

2296
O
HOH
S
74
19.123
53.23
5.431
1.00
37.22

2297
O
HOH
S
75
10.856
22.35
19.47
1.00
19.26

2298
O
HOH
S
76
4.014
20.49
2.2
1.00
37.71

2299
O
HOH
S
78
32.803
10.68
9.175
1.00
22.60

2300
O
HOH
S
79
15.982
27.46
−1.316
1.00
30.63

2301
O
HOH
S
80
6.778
41.32
9.974
1.00
45.09

2302
O
HOH
S
81
6.267
30.45
7.93
1.00
33.02

2303
O
HOH
S
82
19.319
14.91
21.654
1.00
42.45

2304
O
HOH
S
83
2.585
29.42
1.807
1.00
40.89

2305
O
HOH
S
84
2.194
49.14
−16.66
1.00
53.37

2306
O
HOH
S
85
36.352
8.69
3.311
1.00
40.82

2307
O
HOH
S
86
22.685
19.53
29.701
1.00
47.69

2308
O
HOH
S
87
33.974
34.64
0.26
1.00
31.56

2309
O
HOH
S
88
31.744
38.24
1.513
1.00
22.56

2310
O
HOH
S
89
5.825
37.89
6.408
1.00
48.05

2311
O
HOH
S
90
19.49
17.4
−8.965
1.00
38.26

2312
O
HOH
S
91
40.414
35.6
7.949
1.00
35.76

2313
O
HOH
S
92
15.402
46.87
15.762
1.00
39.90

2314
O
HOH
S
93
6.875
29.53
−13.41
1.00
40.19

2315
O
HOH
S
94
8.648
28.6
20.645
1.00
29.73

2316
O
HOH
S
95
22.063
37.44
22.081
1.00
37.50

2317
O
HOH
S
96
27.61
30.94
23.964
1.00
32.74

2318
O
HOH
S
97
10.971
31.16
27.918
1.00
24.96

2319
O
HOH
S
98
26.229
25.48
−11.89
1.00
41.41

2320
O
HOH
S
100
6.704
33.43
−14.58
1.00
36.10

2321
O
HOH
S
101
15.544
8.896
10.723
1.00
33.88

2322
O
HOH
S
102
16.493
16.84
−2.596
1.00
26.55

2323
O
HOH
S
103
28.351
28.27
12.338
1.00
43.77

2324
O
HOH
S
104
27.737
3.455
13.166
1.00
48.23

2325
O
HOH
S
105
24.873
39.51
−19.21
1.00
53.25

2326
O
HOH
S
106
12.972
44.58
−8.54
1.00
25.37

2327
O
HOH
S
107
20.643
61.57
2.015
1.00
57.43

2328
O
HOH
S
108
18.412
21.18
−12.7
1.00
30.69

2329
O
HOH
S
109
21.691
40.71
28.501
1.00
31.23

2330
O
HOH
S
111
37.452
24.33
8.574
1.00
43.15

2331
O
HOH
S
112
28.082
12.03
−2.83
1.00
35.13

2332
O
HOH
S
113
13.626
6.782
9.82
1.00
59.43

2333
O
HOH
S
114
29.219
47.39
−11.5
1.00
33.93

2334
O
HOH
S
115
37.194
25.42
11.265
1.00
49.29

2335
O
HOH
S
116
32.453
24.1
12.149
1.00
37.91

2336
O
HOH
S
117
20.069
18.41
−15.74
1.00
52.69

2337
O
HOH
S
118
37.303
36.57
3.605
1.00
50.95

2338
O
HOH
S
119
26.65
37.93
27.599
1.00
60.19

2339
O
HOH
S
120
40.042
37.14
6.054
1.00
62.83

2340
O
HOH
S
121
16.718
28.82
32.714
1.00
45.22

2341
O
HOH
S
122
15.637
14.39
−3
1.00
32.52

2342
O
HOH
S
123
25.337
43.41
12.302
1.00
46.21

2343
O
HOH
S
124
35.978
27.43
−0.068
1.00
39.51

2344
O
HOH
S
125
33.68
38.72
−6.927
1.00
55.40

2345
O
HOH
S
126
2.654
22.83
6.016
1.00
32.62

2346
O
HOH
S
127
21.42
16.3
32.91
1.00
56.84

2347
O
HOH
S
128
2.525
25.69
7.475
1.00
49.14

2348
O
HOH
S
129
38.283
26.64
7.527
1.00
36.28

2349
O
HOH
S
130
24.339
56.08
−3.205
1.00
42.51

2350
O
HOH
S
131
31.349
39.79
−15.87
1.00
43.44

2351
O
HOH
S
132
14.264
49.95
9.76
1.00
46.86

2352
O
HOH
S
133
29.477
46.34
−15.12
1.00
56.58

2353
O
HOH
S
134
13.24
46.59
14.288
1.00
30.39

2354
O
HOH
S
135
28.713
21.45
14.541
1.00
43.43

2355
O
HOH
S
136
29.863
19.83
16.145
1.00
53.77

2356
O
HOH
S
137
28.691
40.59
0.038
1.00
27.60

2357
O
HOH
S
138
31.992
29.57
17.933
1.00
52.12

2358
O
HOH
S
139
32.346
41.3
−7.206
1.00
48.91

2359
O
HOH
S
140
18.153
37.55
22.932
1.00
31.27

2360
O
HOH
S
141
16.88
57.73
−7.178
1.00
36.07

2361
O
HOH
S
142
3.616
38.62
3.9
1.00
63.76

2362
O
HOH
S
143
18.536
13.34
−5.108
1.00
59.11

2363
O
HOH
S
144
6.14
50.93
−15.59
1.00
38.96

2364
O
HOH
S
145
14.732
25.97
29.458
1.00
32.23

2365
O
HOH
5
146
21.729
19.32
−8.314
1.00
36.70

2366
O
HOH
S
147
8.169
16.53
17.709
1.00
58.27

2367
O
HOH
S
148
11.709
32.98
0.499
1.00
36.22

2368
O
HOH
S
149
13.578
48.33
0.597
1.00
37.61

2369
O
HOH
S
150
12.376
12.47
17.052
1.00
62.89

2370
O
HOH
S
151
9.626
31.89
1.206
1.00
68.72

2371
O
HOH
5
152
28.153
19.15
18.731
1.00
42.30

2372
O
HOH
S
153
32.498
45.94
−7.499
1.00
37.61

2373
O
HOH
S
154
24.755
0.891
18.958
1.00
66.75

2374
O
HOH
S
155
39.681
22.65
2.229
1.00
35.42

2375
O
HOH
S
156
13.536
52.85
2.389
1.00
37.57

2376
O
HOH
S
157
8.317
48.95
2.546
1.00
73.06

2377
O
HOH
S
158
8.644
28.04
−12.59
1.00
33.91

2378
O
HOH
S
159
2.877
30.15
4.135
1.00
62.49

2379
O
HOH
S
160
31.522
7.355
4.7
1.00
35.95

2380
O
HOH
S
161
5.863
26.35
22.68
1.00
39.01

2381
O
HOH
S
162
7.589
46.35
−19.67
1.00
50.76

2382
O
HOH
S
163
22.983
9.848
−2.49
1.00
64.92

2383
O
HOH
S
164
6.674
37.22
8.925
1.00
35.74

2384
O
HOH
S
165
1.66
40.66
10.72
1.00
68.96

2385
O
HOH
S
166
37.85
28.01
11.075
1.00
29.28

2386
O
HOH
S
167
2.367
30.07
11.169
1.00
47.90

2387
O
HOH
S
168
22.807
6.884
24.267
1.00
50.27

2388
O
HOH
S
169
25.253
24.05
−9.518
1.00
56.25

2389
O
HOH
S
170
31.929
40.72
−4.78
1.00
43.99

2390
O
HOH
S
171
29.051
32.12
−14.16
1.00
48.37

2391
O
HOH
S
172
6.854
24.41
13.632
1.00
30.86

2392
O
HOH
S
173
31.121
26.37
−0.287
1.00
26.16

2393
O
HOH
S
174
26.425
4.757
16.289
1.00
46.62

2394
O
HOH
5
175
30.245
52.79
−1.002
1.00
62.86

2395
O
HOH
S
176
11.266
25.3
−15.97
1.00
30.67

2396
O
HOH
S
177
8.232
22.79
−8.256
1.00
36.47

2397
O
HOH
S
178
32.73
30.85
1.133
1.00
29.48

2398
O
HOH
S
179
12.168
13.53
−6.965
1.00
54.81

2399
O
HOH
S
181
9.981
18.58
−15.66
1.00
52.49

2400
O
HOH
S
182
2.592
15.84
3.846
1.00
36.47

2401
O
HOH
S
184
16.07
21.67
25.099
1.00
36.38

2402
O
HOH
S
185
9.58
53.07
5.376
1.00
51.65

2403
O
HOH
S
186
9.863
33.55
29.136
1.00
41.08

2404
O
HOH
S
187
28.882
9.516
−2.636
1.00
43.51

2405
O
HOH
S
188
28.982
14.1
−1.733
1.00
52.94

2406
O
HOH
S
189
8.611
16.55
11.998
1.00
34.51

2407
O
HOH
S
190
12.85
16.63
−1.121
1.00
38.29

2408
O
HOH
S
191
28.378
56.86
−0.306
1.00
70.56

2409
O
HOH
S
192
21.342
14.62
28.328
1.00
75.81

2410
O
HOH
S
193
29.531
7.961
13.212
1.00
47.28

2411
O
HOH
S
194
32.953
32.46
15.308
1.00
53.06

2412
O
HOH
S
195
6.057
23.07
15.892
1.00
44.59

2413
O
HOH
S
196
32.03
19.855
17.068
1.00
61.54

2414
O
HOH
S
197
31.244
15.54
16.59
1.00
47.53

2415
O
HOH
S
198
25.439
9.787
20.81
1.00
55.35

2416
O
HOH
S
199
17.929
17.39
−4.951
1.00
38.99

2417
O
HOH
S
200
20.119
56.57
−12.07
1.00
34.77

2418
O
HOH
S
201
5.206
29.9
4.996
1.00
54.91

2419
O
HOH
S
202
14.253
59.12
−6.767
1.00
57.78

2420
O
HOH
S
203
2.327
36.03
19.271
1.00
71.38

2421
O
HOH
S
205
25.908
29.01
30.674
1.00
45.68

2422
O
HOH
S
206
6.998
27.65
7.373
1.00
33.37

2423
O
HOH
5
207
29.909
10.26
3.633
1.00
28.69

2424
O
HOH
5
208
3.221
39.57
9.013
1.00
64.29

2425
O
HOH
S
209
11.662
26.03
31.453
1.00
30.92

2426
O
HOH
S
210
30.602
43.9
−10.34
1.00
35.47

2427
O
HOH
S
211
5.674
19.99
12.478
1.00
36.93

2428
O
HOH
S
212
8.997
8.066
12.548
1.00
44.27

2429
O
HOH
S
213
18.565
1.299
23.321
1.00
53.87

2430
O
HOH
S
214
14.123
50.52
−14.45
1.00
54.64

2431
O
HOH
S
215
18.959
15.48
28.395
1.00
71.59

2432
O
HOH
S
216
0.665
37.38
17.683
1.00
49.95

2433
O
HOH
S
217
26.863
55.57
−2.207
1.00
46.16

2434
O
HOH
S
218
6.158
22.9
11.742
1.00
31.87

2435
O
HOH
S
219
9.888
16.38
−1.719
1.00
36.68

2436
O
HOH
S
220
30.266
27.84
23.674
1.00
53.45

2437
O
HOH
S
221
30.769
47.55
−1.614
1.00
42.34

2438
O
HOH
S
222
32.195
35.01
15.035
1.00
44.29

2439
O
HOH
S
223
10.286
34.65
−0.758
1.00
25.15

2440
O
HOH
S
224
4.88
17.84
16.029
1.00
58.71

2441
O
HOH
S
225
5.737
41.57
7.23
1.00
41.48

2442
O
HOH
S
226
24.968
27.07
−7.625
1.00
61.37

2443
O
HOH
S
227
26.43
10.73
26.093
1.00
47.70

2444
O
HOH
S
228
9.402
26.41
28.179
1.00
51.51

2445
O
HOH
S
229
22.501
23.96
−9.399
1.00
43.79

2446
O
HOH
S
232
36.306
31.18
7.127
1.00
49.35

2447
O
HOH
S
233
16.063
56.54
4.731
1.00
47.51

2448
O
HOH
S
234
9.113
46
15.205
1.00
51.54

2449
O
HOH
S
236
22.85
16.02
−6.845
1.00
48.61

2450
O
HOH
S
237
4.561
37.73
10.108
1.00
63.61

2451
O
HOH
S
238
8.317
20.22
−8.658
1.00
40.62

2452
O
HOH
S
239
26.545
17.09
26.547
1.00
60.48

2453
O
HOH
S
240
18.438
52.12
−15.97
1.00
68.74

2454
O
HOH
S
241
15.737
11.25
6.148
1.00
40.27

2455
O
HOH
S
242
−2.46
33.66
15.319
1.00
56.63

2456
O
HOH
S
243
9.254
37.42
7.214
1.00
50.70

2457
O
HOH
S
244
22.874
5.448
−0.368
1.00
56.93

2458
O
HOH
S
245
1.408
28.07
19.082
1.00
54.97

2459
O
HOH
S
246
29.407
5.692
12.371
1.00
46.23

2460
O
HOH
S
247
21.392
2.016
21.068
1.00
54.78

2461
O
HOH
S
248
3.142
52.17
−19.3
1.00
61.95

2462
O
HOH
S
249
22.021
57.55
−0.613
1.00
48.17

2463
O
HOH
S
250
13.662
3.611
13.009
1.00
43.82

2464
O
HOH
S
251
19.193
16.6
19.469
1.00
31.39

2465
O
HOH
S
252
3.331
33.52
6.6
1.00
47.67

2466
O
HOH
S
253
10.792
2.983
19.468
1.00
70.14

2467
O
HOH
S
254
16.787
17.52
20.507
1.00
63.73

2468
O
HOH
S
255
2.619
44.64
16.706
1.00
56.53

2469
O
HOH
S
256
27.869
14.32
18.171
1.00
41.98

2470
O
HOH
S
257
31.415
45.49
−13.52
1.00
53.59

2471
O
HOH
S
258
31.255
35.57
−11.97
1.00
33.65

2472
O
HOH
S
259
21.689
4.451
26.354
1.00
52.63

2473
O
HOH
S
260
10.441
20.46
21.585
1.00
35.08

2474
O
HOH
S
261
17.807
18.05
18.034
1.00
49.80

2475
O
HOH
S
262
12.939
41.2
25.86
1.00
49.78

2476
O
HOH
S
263
11.831
38.27
27.695
1.00
41.47

2477
O
HOH
S
264
21.694
14.49
25.644
1.00
49.41

2478
O
HOH
S
265
3.278
19.42
−21.24
1.00
58.93

2479
O
HOH
S
266
32.139
44.55
−1.767
1.00
63.10

2480
O
HOH
S
267
30.536
19.71
26.309
1.00
56.72

2481
O
HOH
S
268
1.033
38.18
8.349
1.00
69.65

2482
O
HOH
S
269
15.677
56.47
−11.13
1.00
45.85

2483
O
HOH
S
270
9.631
49.19
−12.73
1.00
31.76

2484
O
HOH
S
271
26.281
33.95
12.002
1.00
28.74

2485
O
HOH
S
272
16.307
55.36
−6.008
1.00
48.50

2486
O
HOH
S
273
35.226
25.13
1.967
1.00
37.37

2487
O
HOH
S
274
34.15
31.09
10.684
1.00
35.88

2488
O
HOH
S
275
9.81
12.1
−10.1
1.00
42.96

2489
O
HOH
S
277
31.321
17.79
15.555
1.00
54.02

2490
O
HOH
S
278
6.023
17.62
1.258
1.00
32.48

2491
O
HOH
5
279
10.646
28.67
26.826
1.00
33.27

2492
O
HOH
S
280
33.133
28.2
0.795
1.00
32.26

2493
O
HOH
S
281
4.679
49.52
−17.39
1.00
56.01

2494
O
HOH
S
282
19.923
38.29
25.079
1.00
52.01

2495
O
HOH
S
283
17.06
16.72
−7.694
1.00
44.99

2496
O
HOH
S
284
8.155
32.99
31.053
1.00
38.13

2497
O
HOH
S
285
15.353
23.01
31.936
1.00
47.35

2498
O
HOH
S
286
37.587
33.19
10.823
1.00
50.51

2499
O
HOH
S
287
26.366
26.07
14.494
1.00
43.81

2500
O
HOH
S
288
9.308
11.77
3.313
1.00
52.95

2501
O
HOH
5
289
29.889
5.039
4.211
1.00
39.94

2502
O
HOH
S
290
21.608
63.69
5.695
1.00
47.51

2503
O
HOH
S
291
5.878
51.06
−5.441
1.00
57.81

2504
O
HOH
S
292
4.217
31.18
9.122
1.00
34.04

2505
O
HOH
S
293
20.204
52.12
−12.15
1.00
32.14

2506
O
HOH
S
294
31.777
46.88
−9.872
1.00
37.63

2507
O
HOH
S
295
29.367
16.37
18.828
1.00
47.88

2508
O
HOH
S
296
7.053
22.51
23.361
1.00
49.62

2509
O
HOH
S
297
10.448
17.83
24.905
1.00
45.38

2510
O
HOH
S
298
22.727
21.64
−7.856
1.00
44.54

2511
O
HOH
S
299
41.752
38.42
4.331
1.00
51.42

2512
O
HOH
S
300
28.35
29.18
29.86
1.00
35.37

2513
O
HOH
S
301
19.875
8.686
8.347
1.00
36.88

2514
O
HOH
S
302
30.241
47.82
14.46
1.00
52.48

2515
O
HOH
S
303
38.107
31.69
−0.089
1.00
48.80

2516
O
HOH
S
304
29.435
19.53
22.017
1.00
48.53

2517
O
HOH
S
305
28.231
17.78
23.534
1.00
49.19

2518
O
HOH
S
306
25.102
25.86
30.666
1.00
50.04

2519
O
HOH
S
307
20.946
24.31
−13.66
1.00
35.02

2520
O
HOH
S
308
27.296
9.199
14.576
1.00
37.16

2521
O
HOH
S
309
5.593
44.21
15.509
1.00
46.00

2522
O
HOH
S
310
1.445
15.84
16.482
1.00
48.72

2523
O
HOH
S
311
31.898
52.12
−9.291
1.00
36.65

2524
O
HOH
S
312
2.78
26.87
21.407
1.00
37.83

2525
O
HOH
S
313
10.829
21.85
1.47
1.00
38.42

2526
O
HOH
S
314
25.186
43.65
22.198
1.00
39.85

2527
O
HOH
S
315
10.029
44.29
3.158
1.00
61.53

2528
O
HOH
S
316
25.08
12.34
−5.224
1.00
49.90

2529
O
HOH
S
317
24.701
26.06
34.199
1.00
51.37

2530
O
HOH
S
318
17.657
17.78
−11.97
1.00
54.01

2531
O
HOH
S
319
21.669
9.232
−4.594
1.00
50.75

2532
O
HOH
S
320
12.831
30.46
−0.73
1.00
46.31

2533
O
HOH
S
321
−0.839
31.74
16.05
1.00
49.15

2534
O
HOH
S
322
11.333
25.16
29.142
1.00
54.91

2535
O
HOH
S
323
38.448
33.36
4.415
1.00
47.87

2536
O
HOH
S
324
29.755
48.47
−20.47
1.00
61.21

2537
O
HOH
S
325
19.876
22.91
34.487
1.00
53.69

2538
O
HOH
5
326
6.159
6.348
12.404
1.00
45.47

2539
O
HOH
S
327
24.803
24.04
−13.67
1.00
41.36

2540
O
HOH
S
328
34.41
33.84
13.722
1.00
48.67

2541
O
HOH
S
330
28.488
24.85
15.172
1.00
42.44

2542
O
HOH
S
331
18.756
10.01
−0.302
1.00
47.49

2543
O
HOH
S
332
27.919
33.32
15.964
1.00
46.60

2544
O
HOH
S
333
28.084
54.17
−9.919
1.00
47.31

2545
O
HOH
S
334
6.66
20.06
17.321
1.00
66.41

2546
O
HOH
S
335
9.177
51.42
−1.091
1.00
50.92

2547
O
HOH
S
336
26.133
49.98
−13.04
1.00
44.73

2548
O
HOH
S
337
6.461
15
10.655
1.00
50.61

2549
O
HOH
S
338
27.448
21.32
29.977
1.00
46.70

2550
O
HOH
S
339
−2.375
39.03
9.478
1.00
48.95

2551
O
HOH
S
340
39.666
34.71
11.042
1.00
54.77

2552
O
HOH
S
341
31.504
4.157
11.722
1.00
38.27

2553
O
HOH
S
342
30.223
43.44
12.537
1.00
56.22

2554
O
HOH
S
3433
1.793
6.842
14.029
1.00
49.62

2555
O
HOH
S
344
34.165
36.36
−11.48
1.00
54.81

2556
O
HOH
S
345
16.345
29.91
−0.844
1.00
50.86

2557
O
HOH
S
346
16.038
14.04
−0.096
1.00
26.81

2558
O
HOH
S
347
35.56
39.29
6.896
1.00
58.70

2559
O
HOH
S
348
7.207
18.78
−13.36
1.00
48.09

2560
O
HOH
S
349
4.347
25.73
17.608
1.00
48.32

2561
O
HOH
S
350
23.981
49.9
20.29
1.00
45.46

2562
O
HOH
S
351
−1.311
39.18
20.561
1.00
47.06

2563
O
HOH
S
352
29.438
35.08
−13.57
1.00
51.53

2564
O
HOH
S
353
22.157
11.96
−8.267
1.00
58.38

2565
O
HOH
S
354
28.535
23.39
−8.407
1.00
38.50

2566
O
HOH
S
355
16.02
7.615
25.043
1.00
63.84

2567
O
HOH
S
356
2.323
34.05
2.822
1.00
52.94

2568
O
HOH
S
357
14.88
19.56
25.915
1.00
44.98

2569
O
HOH
S
358
33.923
47.33
−12.62
1.00
52.85

2570
O
HOH
S
359
27.496
24.78
30.413
1.00
48.33

2571
O
HOH
S
360
20.476
43.25
26.095
1.00
52.94

2572
O
HOH
S
361
28.282
37.79
30.539
1.00
62.99

2573
O
HOH
S
362
27.472
34.09
−15.38
1.00
50.71

2574
O
HOH
S
363
25.666
34.54
30.416
1.00
54.08

2575
O
HOH
S
364
29.779
1.14
1.301
1.00
59.34

2576
O
HOH
S
365
5.434
39.02
22.161
1.00
47.10

2577
O
HOH
S
366
5.05
16.76
20.069
1.00
60.26

2578
O
HOH
S
367
18.636
55.72
−4.804
1.00
55.62

2579
O
HOH
S
368
32.684
59.06
10.827
1.00
39.90

2580
O
HOH
S
369
28.244
51.07
−11.91
1.00
52.57

2581
O
HOH
S
370
11.589
51.23
−1.777
1.00
63.06

2582
O
HOH
S
371
2.98
19.43
−24.51
1.00
45.57

2583
O
HOH
S
372
22.088
60
−1.466
1.00
61.45

2584
O
HOH
S
373
22.665
43.26
31.048
1.00
47.28

2585
O
HOH
S
374
30.445
38.97
29.886
1.00
57.25

2586
O
HOH
S
375
35.859
38.01
1.977
1.00
61.81

2587
O
HOH
S
376
6.112
31.91
−17.26
1.00
49.61

2588
O
HOH
S
377
6.721
15.6
−22.4
1.00
59.42

2589
O
HOH
S
378
12.118
1.192
18.305
1.00
48.35

2590
O
HOH
S
379
4.24
32.09
1.805
1.00
44.18

2591
O
HOH
S
380
29.696
35.08
27.75
1.00
55.76

2592
O
HOH
S
381
26.359
7.481
25.027
1.00
51.90

2593
O
HOH
S
382
9.133
46.89
3.888
1.00
56.70

2594
O
HOH
S
383
10.643
46.44
−20.34
1.00
37.21

2595
O
HOH
S
384
8.232
48.96
17.207
1.00
59.01

2596
O
HOH
S
385
20.326
15.01
−8.821
1.00
55.36

2597
O
HOH
S
386
19.253
−0.131
16.57
1.00
45.30

2598
O
HOH
S
387
7.34
49.8
−0.68
1.00
55.02

2599
O
HOH
S
388
2.512
47.88
0.707
1.00
48.12

2600
O
HOH
S
389
13.153
54.6
−2.131
1.00
53.44

2601
O
HOH
S
390
17.487
16.51
30.198
1.00
49.11

2602
O
HOH
S
391
20.116
10.78
23.265
1.00
55.34

2603
O
HOH
S
392
23.496
12.69
26.104
1.00
62.62

2604
O
HOH
S
393
20.396
47.11
12.135
1.00
51.92

2605
O
HOH
S
394
9.042
10.92
17.744
1.00
57.21

2606
O
HOH
S
395
15.086
15.2
30.474
1.00
56.74

2607
O
HOH
S
396
27.824
7.29
−8.552
1.00
49.75

2608
O
HOH
S
397
−1.167
31.36
18.711
1.00
53.14

2609
O
HOH
S
398
7.302
35.54
28.016
1.00
61.44

2610
O
HOH
S
399
14.214
16.7
−13.22
1.00
42.98

2611
O
HOH
S
400
20.092
59.9
−2.921
1.00
54.66

2612
O
HOH
S
401
28.927
1.994
14.98
1.00
47.04

2613
O
HOH
S
402
14.185
28.7
31.582
1.00
59.65

2614
O
HOH
S
403
20.834
52.48
14.019
1.00
61.68

2615
O
HOH
S
404
13.279
5.355
25.439
1.00
52.09

2616
O
HOH
5
405
26.886
59.65
−2.846
1.00
46.54

2617
O
HOH
S
406
11.357
5.386
16.734
1.00
45.29

2618
O
HOH
S
407
30.634
57.68
11.14
1.00
63.95

2619
O
HOH
S
408
33.859
39.18
−13.25
1.00
54.28

2620
O
HOH
S
409
16.114
14.41
−7.014
1.00
46.14

2621
O
HOH
S
410
37.72
38.28
6.176
1.00
64.28

2622
O
HOH
S
411
6.555
42.04
−19.44
1.00
48.56

2623
C1A
735
C
1
19.341
40.73
3.993
1.00
15.91

2624
O1C
735
C
1
18.239
40.2
4.31
1.00
17.26

2625
O1B
735
C
1
20.381
40.5
4.658
1.00
17.17

2626
C1D
735
C
1
19.457
41.69
2.755
1.00
14.73

2627
C1X
735
C
1
19.835
43.1
3.255
1.00
16.66

2628
CIY
735
C
1
18.085
41.87
1.978
1.00
16.99

2629
O1E
735
C
1
20.62
41.22
1.905
1.00
15.62

2630
C1F
735
C
1
20.412
40.1
1.046
1.00
12.70

2631
G1G
735
C
1
20.444
40.32
−0.337
1.00
16.64

2632
C11
735
C
1
20.235
39.25
−1.206
1.00
15.86

2633
C1K
735
C
1
19.982
37.9
−0.694
1.00
15.12

2634
C1J
735
C
1
19.956
37.68
0.701
1.00
15.25

2635
C1H
735
C
1
20.17
38.77
1.574
1.00
16.34

2636
C1L
735
C
1
19.737
36.71
−1.661
1.00
16.46

2637
N1M
735
C
1
19.038
37.26
−2.855
1.00
16.48

2638
C2A
735
C
1
17.688
37.38
−3.024
1.00
19.45

2639
O2A
735
C
1
16.891
37
−2.138
1.00
20.40

2640
S2C
735
C
1
15.434
38.08
−4.377
1.00
18.50

2641
C2B
735
C
1
17.146
37.95
−4.199
1.00
18.76

2642
C2D
735
C
1
17.789
38.48
−5.386
1.00
19.70

2643
C20
735
C
1
19.304
38.59
−5.689
1.00
20.26

2644
N2E
735
C
1
16.929
38.94
−6.305
1.00
17.68

2645
C2F
735
C
1
15.613
38.79
−5.935
1.00
19.94

2646
G2H
735
C
1
14.527
39.19
−6.734
1.00
21.71

2647
C2J
735
C
1
13.172
39
−6.28
1.00
20.47

2648
C2L
735
C
1
12.08
39.39
−7.09
1.00
22.73

2649
C2M
735
C
1
12.3
39.99
−8.38
1.00
20.47

2650
C2K
735
C
1
13.648
40.19
−8.827
1.00
23.90

2651
C2I
735
C
1
14.733
39.8
−8.026
1.00
22.13

2652
C2N
735
C
1
11.109
40.43
−9.297
1.00
25.97

2653
F2P
735
C
1
10.97
39.5
−10.3
1.00
31.88

2654
F2Q
735
C
1
9.921
40.5
−8.624
1.00
31.88

2655
F2O
735
C
1
11.341
41.65
−9.859
1.00
31.88

[0390]

7

TABLE 4

[0391] It will be understood that various details of the invention may be changed without departing from the scope of the invention. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation—the invention being defined by the claims.

CRYSTALLIZED PPARa LIGAND BINDING DOMAIN POLYPEPTIDE AND SCREENING METHODS EMPLOYING SAME

Information

Publication Number

Date Filed

Date Published

Inventors

CPC

US Classifications

International Classifications

Abstract

Description

Claims

PCT Information