Claims
- 1. A method for identifying desirable protein backbone configurations comprising:
generating backbone protein configurations using a set of dihedral angle pairs; normalizing the total surface exposure of each remaining configuration; generating a random set of sequences of hydrophobicities with uniform weight on the space of allowed sequences; determining, for each randomly generated sequence, which of the remaining configurations is the ground state, and; recording a ground-state configuration for each sequence wherein the desirable configurations are those containing the most sequences with that configuration as their ground state.
- 2. A method for identifying desirable protein backbone configurations as in claim 1 wherein:
one pair of dihedral angle pairs corresponds to an alpha helix and one pair of dihedral angle pairs corresponds to a beta strand.
- 3. A method for identifying desirable protein backbone configurations as in claim 1 wherein:
two sets of dihedral angles correspond to an alpha helix and one set of dihedral angle pairs corresponds to a beta strand.
- 4. A method for identifying desirable protein backbone configurations as in claim 3 wherein:
additional dihedral angles fall within regions of high frequency in a Ramachandran plot.
- 5. A method for identifying desirable protein backbone configurations as in claim 4 wherein:
the probability of choosing a particular pair of dihedral angles depends on the preceeding pairs of dihedral angles along the backbone.
- 6. A method for identifying desirable protein backbone configurations as in claim 5 further comprising:
eliminating self-intersecting configurations.
- 7. A method for identifying desirable protein backbone configurations as in claim 6 further comprising:
eliminating non-compact configurations.
- 8. A method for identifying desirable protein backbone configurations as in claim 7 further comprising:
clustering configurations sufficiently similar in the three dimensional trajectory followed by their backbones and treating all configurations within a cluster as variants of a single configuration, and; summing, for all configurations in a cluster, the number of sequences with that configuration as their ground state such that the sum is considered the designability of the cluster.
- 9. A method for identifying desirable protein backbone configurations as in claim 8 further comprising:
eliminating configurations with low Variances.
- 10. A method for identifying desirable protein backbone configurations as in claim 1 wherein:
the set of dihedral angle pairs is a set of strings of dihedral angle pairs.
- 11. A method for identifying desirable protein backbone configurations as in claim 10 wherein:
the strings of angles are weighted according to their frequency of appearance in natural proteins and infrequent strings are eliminated.
- 12. A method for identifying desirable protein backbone configurations as in claim 1 wherein:
normalizing is accomplished by dividing the surface exposure of each amino acid in a given configuration by the total surface exposure of that configuration.
- 13. A method for identifying desirable protein backbone configurations as in claim 1 further comprising:
eliminating configurations with low Variance.
- 14. A method for identifying desirable protein backbone configurations as in claim 1 further comprising:
eliminating self-intersecting configurations.
- 15. A method for identifying desirable protein backbone configurations as in claim 14 further comprising:
eliminating non-compact configurations.
- 16. A method for identifying desirable protein backbone configurations as in claim 1 further comprising:
eliminating non-compact configurations.
- 17. A method for identifying desirable protein backbone configurations as in claim 1 further comprising:
eliminating configurations with low Variance.
- 18. A method for identifying desirable protein backbone configurations as in claim 1 further comprising:
eliminating all configurations that are not favorable for forming a large number of hydrogen bonds after eliminating non-compact configurations.
- 19. A method for identifying desirable protein backbone configurations as in claim 1 further comprising:
clustering configurations sufficiently similar in the three dimensional trajectory followed by their backbones and treating all configurations within a cluster as variants of a single configuration, and; summing, for all configurations in a cluster, the number of sequences with that configuration as their ground state such that the sum is considered the designability of the cluster.
- 20. A method for identifying desirable protein backbone configurations as in claim 19 wherein:
clustering is accomplished by totaling the root-mean-square distance between every pair of configurations and defining a configuration as a member of a cluster if it lies within a root-mean-square distance X of any member of the cluster.
- 21. A method for identifying desirable protein backbone configurations as in claim 20 wherein:
λ is 0.4 Å per amino acid.
- 22. A method for designing proteins comprising:
generating backbone protein configurations using a set of dihedral angle pairs; eliminating self-intersecting configurations; normalizing the total surface exposure of each remaining configuration; generating a random set of sequences of hydrophobicities with uniform weight on the space of allowed sequences for each remaining configuration; determining, for each randomly generated sequence, which of the remaining configurations is the ground state; recording the ground-state configuration for each sequence wherein desirable configurations are those containing the most sequences with that configuration as their ground state, and; synthesizing sequences of amino acids for the desirable configurations.
- 23. A method for designing proteins as in claim 22 wherein:
one set of dihedral angle pairs corresponds to an alpha helix and one set of dihedral angles corresponds to a beta strand.
- 24. A method for designing proteins as in claim 22 wherein:
two sets of dihedral angles correspond to an alpha helix and one set of dihedral angle pairs corresponds to a beta strand.
- 25. A method for designing proteins as in claim 24 wherein:
additional dihedral angle pairs fall within regions of high frequency in a Ramachandran plot.
- 26. A method for designing proteins as in claim 25 wherein:
the probability of choosing a particular pair of dihedral angles depends on the preceeding pairs of dihedral angles along the backbone.
- 27. A method for designing proteins as in claim 26 further comprising:
eliminating self-intersecting configurations.
- 28. A method for designing proteins as in claim 27 further comprising:
eliminating non-compact configurations.
- 29. A method for designing proteins as in claim 28 further comprising:
clustering configurations sufficiently similar in the three dimensional trajectory followed by their backbones and treating all configurations within a cluster as variants of a single configuration, and; summing, for all configurations in a cluster, the number of sequences with that configuration as their ground state such that the sum is considered the designability of the cluster.
- 30. A method for designing proteins as in claim 29 further comprising:
recording the Variance of each configuration, ranking the configurations from highest Variance to lowest, and designing proteins starting with the configurations having the highest Variance.
- 31. A method for designing proteins as in claim 22 wherein:
the set of dihedral angles is a set of strings of dihedral angles.
- 32. A method for designing proteins as in claim 31 wherein:
the strings of angles are weighted according to their frequency of appearance in natural proteins and infrequent strings are eliminated.
- 33. A method for designing proteins as in claim 22 wherein:
normalizing is accomplished by dividing the surface exposure of each amino acid in a given configuration by the total surface exposure of that configuration.
- 34. A method for designing proteins as in claim 22 further comprising:
recording the Variance of each configuration, ranking the configurations from highest Variance to lowest, and designing proteins starting with the configurations having the highest Variance.
- 35. A method for designing proteins as in claim 22 further comprising:
eliminating non-compact configurations after self-intersecting configurations are eliminated.
- 36. A method for designing proteins as in claim 35 further comprising:
clustering configurations sufficiently similar in the three dimensional trajectory followed by their backbones and treating all configurations within a cluster as variants of a single configuration ration, and; summing, for all configurations in a cluster, the number of sequences with that configuration as their ground state such that the sum is considered the designability of the cluster.
- 37. A method for designing proteins as in claim 22 further comprising:
eliminating all configurations that are not favorable for forming hydrogen bonds after eliminating non-compact configurations.
- 38. A method for designing proteins as in claim 22 further comprising:
clustering configurations sufficiently similar in the three dimensional trajectory followed by their backbones and treating all configurations within a cluster as variants of a single configuration, and; summing, for all configurations in a cluster, the number of sequences with that configuration as their ground state such that the sum is considered the designability of the cluster.
- 39. A method for designing proteins as in claim 38 wherein:
clustering is accomplished by totaling the root-mean-square distance between every pair of configurations and defining a configuration as a member of a cluster if it lies within a root-mean-square distance λ of any member of the cluster.
- 40. A method for designing proteins as in claim 39 wherein:
λ is 0.4 Angstroms per amino acid.
- 41. A method for analyzing the designability of protein backbone configurations to determine if the number of sequences each configuration has in its ground state is larger than a predetermined number comprising:
generating backbone protein configurations using a set of dihedral angle pairs; eliminating self-intersecting configurations; normalizing the total surface exposure of each remaining configuration; generating a random set of sequences of hydrophobicities with uniform weight on the space of allowed sequences; determining, for each randomly generated sequence, which of the remaining configurations is the ground state; recording a ground-state configuration for each sequence wherein the desirable configurations are those containing the most sequences with that configuration as their ground state, and; comparing how many sequences each configuration has in its ground-state with the predetermined number whereby configurations with larger numbers are highly designable.
- 42. A method for analyzing the designability of protein backbone configurations as in claim 41 wherein:
normalizing is accomplished by dividing the surface exposure of each amino acid in a given configuration by the total surface exposure of that configuration.
- 43. A method for analyzing the designability of protein backbone configurations as in claim 41 wherein:
one set of dihedral angle pairs corresponds to an alpha helix and one set of dihedral angle pairs corresponds to a beta strand.
- 44. A method for analyzing the designability of protein backbone configurations as in claim 41 wherein:
two sets of dihedral angle pairs correspond to an alpha helix and one set of dihedral angle pairs corresponds to a beta strand.
- 45. A method for analyzing the designability of protein backbone configurations as in claim 44 wherein:
additional dihedral angles fall within regions of high frequency in a Ramachandran plot.
- 46. A method for analyzing the designability of protein backbone configurations as in claim 45 wherein:
the probability of choosing a particular pair of dihedral angles depends on the preceeding pairs of dihedral angles along the backbone.
- 47. A method for analyzing the designability of protein backbone configurations as in claim 46 further comprising:
eliminating non-compact configurations after self-intersecting configurations are eliminated.
- 48. A method for analyzing the designability of protein backbone configurations as in claim 47 further comprising:
recording the Variance of each configuration, ranking the configurations from highest Variance to lowest, and designing proteins starting with the configurations having the highest Variance.
- 49. A method for analyzing the designability of protein backbone configurations as in claim 48 further comprising:
clustering configurations sufficiently similar in the three dimensional trajectory followed by their backbones and treating all configurations within a cluster as variants of a single configuration, and; summing, for all configurations in a cluster, the number of sequences with that configuration as their ground state such that the sum is considered the designability of the cluster.
- 50. A method for analyzing the designability of protein backbone configurations as in claim 41 wherein:
the set of dihedral angle pairs is a set of strings of dihedral angle pairs.
- 51. A method for analyzing the designability of protein backbone configurations as in claim 49 wherein:
the strings of angles are weighted according to their frequency of appearance in natural proteins and infrequent strings are eliminated.
- 52. A method for analyzing the designability of protein backbone configurations as in claim 41 wherein:
the probability of choosing a particular pair of dihedral angles depends on the preceeding pairs of dihedral angles along the backbone.
- 53. A method for analyzing the designability of protein backbone configurations as in claim 41 further comprising:
recording the Variance of each configuration, ranking the configurations from highest Variance to lowest, and designing proteins starting with the configurations having the highest Variance.
- 54. A method for analyzing the designability of protein backbone configurations as in claim 41 further comprising:
eliminating all configurations that are not favorable for forming a large number of hydrogen bonds after eliminating non-compact configurations.
- 55. A method for analyzing the designability of protein backbone configurations as in claim 41 further comprising:
clustering configurations sufficiently similar in the three dimensional trajectory followed by their backbones and treating all configurations within a cluster as variants of a single configuration, and; summing, for all configurations in a cluster, the number of sequences with that configuration as their ground state such that the sum is considered the designability of the cluster.
- 56. A method for analyzing the designability of protein backbone configurations as in claim 55 further comprising:
clustering is accomplished by totaling the root-mean-square distance between every pair of configurations and defining a configuration as a member of a cluster if it lies within a root-mean-square distance λ of any member of the cluster.
- 57. A method for analyzing the designability of protein backbone configurations as in claim 56 further comprising:
λ is 0.4 Angstroms per amino acid.
CROSS REFERENCES TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Applications, Ser. Nos. 60/240,745 and 60/240,747 filed on Oct. 16, 2000.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60240745 |
Oct 2000 |
US |
|
60240747 |
Oct 2000 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09730214 |
Dec 2000 |
US |
Child |
10093108 |
Mar 2002 |
US |