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. 1993 May;2(5):762–785. doi: 10.1002/pro.5560020508

Reduced representation model of protein structure prediction: statistical potential and genetic algorithms.

S Sun 1
PMCID: PMC2142494  PMID: 8495198

Abstract

A reduced representation model, which has been described in previous reports, was used to predict the folded structures of proteins from their primary sequences and random starting conformations. The molecular structure of each protein has been reduced to its backbone atoms (with ideal fixed bond lengths and valence angles) and each side chain approximated by a single virtual united-atom. The coordinate variables were the backbone dihedral angles phi and psi. A statistical potential function, which included local and nonlocal interactions and was computed from known protein structures, was used in the structure minimization. A novel approach, employing the concepts of genetic algorithms, has been developed to simultaneously optimize a population of conformations. With the information of primary sequence and the radius of gyration of the crystal structure only, and starting from randomly generated initial conformations, I have been able to fold melittin, a protein of 26 residues, with high computational convergence. The computed structures have a root mean square error of 1.66 A (distance matrix error = 0.99 A) on average to the crystal structure. Similar results for avian pancreatic polypeptide inhibitor, a protein of 36 residues, are obtained. Application of the method to apamin, an 18-residue polypeptide with two disulfide bonds, shows that it folds apamin to native-like conformations with the correct disulfide bonds formed.

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Selected References

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  1. Anfinsen C. B. Principles that govern the folding of protein chains. Science. 1973 Jul 20;181(4096):223–230. doi: 10.1126/science.181.4096.223. [DOI] [PubMed] [Google Scholar]
  2. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  3. Blommers M. J., Lucasius C. B., Kateman G., Kaptein R. Conformational analysis of a dinucleotide photodimer with the aid of the genetic algorithm. Biopolymers. 1992 Jan;32(1):45–52. doi: 10.1002/bip.360320107. [DOI] [PubMed] [Google Scholar]
  4. Blundell T. L., Pitts J. E., Tickle I. J., Wood S. P., Wu C. W. X-ray analysis (1. 4-A resolution) of avian pancreatic polypeptide: Small globular protein hormone. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4175–4179. doi: 10.1073/pnas.78.7.4175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chan H. S., Dill K. A. Origins of structure in globular proteins. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6388–6392. doi: 10.1073/pnas.87.16.6388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chan H. S., Dill K. A. Polymer principles in protein structure and stability. Annu Rev Biophys Biophys Chem. 1991;20:447–490. doi: 10.1146/annurev.bb.20.060191.002311. [DOI] [PubMed] [Google Scholar]
  7. Covell D. G., Jernigan R. L. Conformations of folded proteins in restricted spaces. Biochemistry. 1990 Apr 3;29(13):3287–3294. doi: 10.1021/bi00465a020. [DOI] [PubMed] [Google Scholar]
  8. Crippen G. M., Viswanadhan V. N. Sidechain and backbone potential function for conformational analysis of proteins. Int J Pept Protein Res. 1985 May;25(5):487–509. doi: 10.1111/j.1399-3011.1985.tb02203.x. [DOI] [PubMed] [Google Scholar]
  9. Freeman C. M., Catlow C. R., Hemmings A. M., Hider R. C. The conformation of apamin. FEBS Lett. 1986 Mar 3;197(1-2):289–296. doi: 10.1016/0014-5793(86)80344-1. [DOI] [PubMed] [Google Scholar]
  10. Hagler A. T., Honig B. On the formation of protein tertiary structure on a computer. Proc Natl Acad Sci U S A. 1978 Feb;75(2):554–558. doi: 10.1073/pnas.75.2.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Heringa J., Argos P. Side-chain clusters in protein structures and their role in protein folding. J Mol Biol. 1991 Jul 5;220(1):151–171. doi: 10.1016/0022-2836(91)90388-m. [DOI] [PubMed] [Google Scholar]
  12. Huyghues-Despointes B. M., Nelson J. W. Stabilities of disulfide bond intermediates in the folding of apamin. Biochemistry. 1992 Feb 11;31(5):1476–1483. doi: 10.1021/bi00120a026. [DOI] [PubMed] [Google Scholar]
  13. Kuntz I. D., Crippen G. M., Kollman P. A., Kimelman D. Calculation of protein tertiary structure. J Mol Biol. 1976 Oct 5;106(4):983–994. doi: 10.1016/0022-2836(76)90347-8. [DOI] [PubMed] [Google Scholar]
  14. Lau K. F., Dill K. A. Theory for protein mutability and biogenesis. Proc Natl Acad Sci U S A. 1990 Jan;87(2):638–642. doi: 10.1073/pnas.87.2.638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Levitt M. A simplified representation of protein conformations for rapid simulation of protein folding. J Mol Biol. 1976 Jun 14;104(1):59–107. doi: 10.1016/0022-2836(76)90004-8. [DOI] [PubMed] [Google Scholar]
  16. Levitt M., Warshel A. Computer simulation of protein folding. Nature. 1975 Feb 27;253(5494):694–698. doi: 10.1038/253694a0. [DOI] [PubMed] [Google Scholar]
  17. Pincus M. R., Klausner R. D., Scheraga H. A. Calculation of the three-dimensional structure of the membrane-bound portion of melittin from its amino acid sequence. Proc Natl Acad Sci U S A. 1982 Aug;79(16):5107–5110. doi: 10.1073/pnas.79.16.5107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ramachandran G. N., Sasisekharan V. Conformation of polypeptides and proteins. Adv Protein Chem. 1968;23:283–438. doi: 10.1016/s0065-3233(08)60402-7. [DOI] [PubMed] [Google Scholar]
  19. Shakhnovich E. I., Gutin A. M. Implications of thermodynamics of protein folding for evolution of primary sequences. Nature. 1990 Aug 23;346(6286):773–775. doi: 10.1038/346773a0. [DOI] [PubMed] [Google Scholar]
  20. Srinivasan N., Sowdhamini R., Ramakrishnan C., Balaram P. Conformations of disulfide bridges in proteins. Int J Pept Protein Res. 1990 Aug;36(2):147–155. doi: 10.1111/j.1399-3011.1990.tb00958.x. [DOI] [PubMed] [Google Scholar]
  21. Sun S., Luo N., Ornstein R. L., Rein R. Protein structure prediction based on statistical potential. Biophys J. 1992 Apr;62(1):104–106. doi: 10.1016/S0006-3495(92)81793-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Taketomi H., Kanô F., Go N. The effect of amino acid substitution on protein-folding and -unfolding transition studied by computer simulation. Biopolymers. 1988 Apr;27(4):527–559. doi: 10.1002/bip.360270402. [DOI] [PubMed] [Google Scholar]
  23. Taketomi H., Ueda Y., Gō N. Studies on protein folding, unfolding and fluctuations by computer simulation. I. The effect of specific amino acid sequence represented by specific inter-unit interactions. Int J Pept Protein Res. 1975;7(6):445–459. [PubMed] [Google Scholar]
  24. Tanaka S., Scheraga H. A. Medium- and long-range interaction parameters between amino acids for predicting three-dimensional structures of proteins. Macromolecules. 1976 Nov-Dec;9(6):945–950. doi: 10.1021/ma60054a013. [DOI] [PubMed] [Google Scholar]
  25. Terwilliger T. C., Eisenberg D. The structure of melittin. II. Interpretation of the structure. J Biol Chem. 1982 Jun 10;257(11):6016–6022. [PubMed] [Google Scholar]
  26. Tuffery P., Etchebest C., Hazout S., Lavery R. A new approach to the rapid determination of protein side chain conformations. J Biomol Struct Dyn. 1991 Jun;8(6):1267–1289. doi: 10.1080/07391102.1991.10507882. [DOI] [PubMed] [Google Scholar]
  27. Unger R., Harel D., Wherland S., Sussman J. L. A 3D building blocks approach to analyzing and predicting structure of proteins. Proteins. 1989;5(4):355–373. doi: 10.1002/prot.340050410. [DOI] [PubMed] [Google Scholar]
  28. Wemmer D., Kallenbach N. R. Structure of apamin in solution: a two-dimensional nuclear magnetic resonance study. Biochemistry. 1983 Apr 12;22(8):1901–1906. doi: 10.1021/bi00277a025. [DOI] [PubMed] [Google Scholar]
  29. Wilson C., Doniach S. A computer model to dynamically simulate protein folding: studies with crambin. Proteins. 1989;6(2):193–209. doi: 10.1002/prot.340060208. [DOI] [PubMed] [Google Scholar]

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