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Fold Recognition using the OPLS All-Atom Potential and the Surface Generalized Born Solvent Model

  • Anthony K. Felts
  • Anders Wallqvist
  • Emilio Gallicchio
  • Donna Bassolino
  • Stanley R. Krystek
  • Ronald M. Levy
Conference paper
Part of the Lecture Notes in Computational Science and Engineering book series (LNCSE, volume 24)

Abstract

Protein decoy data sets provide a benchmark for testing scoring functions designed for fold recognition and protein homology modeling problems. It is commonly believed that statistical potentials based on reduced atomic models are better able to discriminate native-like from misfolded decoys than scoring functions based on more detailed molecular mechanics models. Recent benchmark tests, however, suggest otherwise. Further analysis of the effectiveness of all atom molecular mechanics scoring functions for detecting misfolded decoys and direct comparison with results obtained using a statistical potential derived for a reduced atomic model are presented in this report. The OPLS all-atom force field is used as a scoring function to detect native protein folds among the Park & Levitt large decoy sets. Solvent electrostatic effects are included through the Surface Generalized Born (SGB) model. The OPLS potential with SGB solvation (OPLS-AA/SGB) provides good discrimination between native-like structures and non-native decoys. From an analysis of the individual energy components of the OPLS-AA/SGB potential for the native and the best-ranked decoy, it is determined that a roughly even balance of the terms of the potential is responsible for distinguishing the native from the misfolded conformations. Different combinations of individual energy terms provide less discrimination than the total energy. The effects of scoring decoys using several dielectric models are compared also. With the SGB solvation model, close to 100% of the structures with energies within 100 kcal/mol of the native state minimum are native-like. In contrast, only 20% of the low energy structures are found to be native-like when a distance dependent dielectric is used instead of SGB to model solvent electrostatic effects. The results are consistent with observations that all-atom molecular potentials coupled with intermediate level solvent dielectric models are competitive with knowledge-based potentials for decoy detection and protein modeling problems such as fold recognition.

Keywords

Protein decoys homology modeling protein solvation fold recognition 

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References

  1. 1.
    Lazaridis, T.; Karplus, M. Curr. Opin. Struct. Biol. 2000, 10, 139–145.PubMedCrossRefGoogle Scholar
  2. 2.
    Wodak, S. J.; Rooman, M. J. Curr. Opin. Struct. Biol. 1993, 3, 247–259.CrossRefGoogle Scholar
  3. 3.
    Jones, D. T.; Thornton, J. M. Curr. Opin. Struct. Biol. 1996, 6, 210–216.PubMedCrossRefGoogle Scholar
  4. 4.
    Plaxco, K. W.; Riddle, D. S.; Grantcharova, V.; Baker, D. Curr. Opin. Struct. Biol. 1998, 8, 80–85.PubMedCrossRefGoogle Scholar
  5. 5.
    Hao, M.; Scheraga, H. A. Curr. Opin. Struct. Biol. 1999, 9, 184–188.PubMedCrossRefGoogle Scholar
  6. 6.
    Osguthorpe, D. J. Curr. Opin. Struct. Biol. 2000, 10, 146–152.PubMedCrossRefGoogle Scholar
  7. 7.
    Eyrich, V.; Standley, D.; Felts, A.; Friesner, R. Proteins: Struct. Fund. Genet. 1999, 35, 41–57.CrossRefGoogle Scholar
  8. 8.
    Rick, S. W.; Berne, B. J.  J. Am. Chem. Soc. 1994, 116, 3949–3954.Google Scholar
  9. 9.
    Levy, R. M.; Gallicchio, E. Annu. Rev. Phys. Chem. 1998, 49, 531–567.PubMedCrossRefGoogle Scholar
  10. 10.
    Rashin, A. A.; Bukatin, M. A. J. Phys. Chem. 1994, 98, 386–389.CrossRefGoogle Scholar
  11. 11.
    Sitkoff, D.; Sharp, K. A.; Honig, B. J. Phys. Chem. 1994, 98, 1978–1988.CrossRefGoogle Scholar
  12. 12.
    Tannor, D. J.; Marten, B.; Murphy, R.; Friesner, R. A.; Sitkoff, D.; Nicholls, A.; Ringnalda, M.; Goddard, III, W. A.; Honig, B. J. Am. Chem. Soc. 1994, 116, 11875–11882.CrossRefGoogle Scholar
  13. 13.
    Sitkoff, D.; Ben-Tal, N.; Honig, B. J. Phys. Chem. 1996, 100, 2744–2752.CrossRefGoogle Scholar
  14. 14.
    Hawkins, G.; Cramer, C.; Truhlar, D. J. Phys. Chem. 1996, 100, 19824–19839.CrossRefGoogle Scholar
  15. 15.
    Gallicchio, E.; Zhang, L.; Levy, R. M. 2001, In preparation.Google Scholar
  16. 16.
    Eisenberg, D.; McLachlan, A. D. Nature 1986, 319, 199–203.PubMedCrossRefGoogle Scholar
  17. 17.
    Holm, L.; Sander, C. J. Mol. Biol. 1992, 225, 93–105.PubMedCrossRefGoogle Scholar
  18. 18.
    van Gunsteren, W. F.; Luque, F. J.; Timms, D.; Torda, A. E. Annu. Rev. Biophys. Biomol.Struct. 1994, 23, 847–863.PubMedCrossRefGoogle Scholar
  19. 19.
    Smith, P. E.; Pettitt, B. M. J. Phys. Chem. 1994, 98, 9700–9711.CrossRefGoogle Scholar
  20. 20.
    Monge, A.; Lathrop, E. J. P.; Gunn, J. R.; Shenkin, P. S.; Friesner, R. A. J. Mol. Biol. 1995, 247, 995–1012.PubMedCrossRefGoogle Scholar
  21. 21.
    Schaefer, M.; van Vlijmen, H. W.; Karplus, M. Advances in Protein Chemistry 1998, 51, 1–57.PubMedCrossRefGoogle Scholar
  22. 22.
    Lazaridis, T.; Karplus, M. J. Mol. Biol. 1999, 288, 477–487.PubMedCrossRefGoogle Scholar
  23. 23.
    Vorobjev, Y. N.; Hermans, J. Biophys. Chem. 1999, 78, 195–205.PubMedCrossRefGoogle Scholar
  24. 24.
    Gilson, M. K.; Honig, B. Proteins: Struct. Fund. Genet. 1988, 4, 7–18.CrossRefGoogle Scholar
  25. 25.
    Bashford, D.; Karplus, M. Biochemistry 1990, 29, 10219–10225.PubMedCrossRefGoogle Scholar
  26. 26.
    Rashin, A. A. J. Phys. Chem. 1990, 94, 1725–1733.CrossRefGoogle Scholar
  27. 27.
    Sharp, K. A.; Honig, B. Annu. Rev. Biophys. Chem. 1990, 19, 301–332.CrossRefGoogle Scholar
  28. 28.
    Warshel, A.; Åqvist, J. Annu. Rev. Biophys. Chem. 1991, 20, 267–298.CrossRefGoogle Scholar
  29. 29.
    Gilson, M. K.; Davis, M. E.; Luty, B. A.; McCammon, J. A. J. Phys. Chem. 1993, 97, 3591–3600.CrossRefGoogle Scholar
  30. 30.
    Honig, B.; Sharp, K.; Yang, A.-S. J. Phys. Chem. 1993, 97, 1101–1109.CrossRefGoogle Scholar
  31. 31.
    Mohan, V.; Davis, M. E.; McCammon, J. A.; Pettitt, B. M. J. Phys. Chem. 1992, 96, 6428–6431.CrossRefGoogle Scholar
  32. 32.
    Simonson, T.; Brünger, A. T. J. Phys. Chem. 1994, 98, 4683–4694.CrossRefGoogle Scholar
  33. 33.
    Ösapay, K.; Young, W. S.; Bashford, D.; Brooks III, C.L.; Case, D. A. J. Phys. Chem. 1996, 100, 2698–2705.CrossRefGoogle Scholar
  34. 34.
    Edinger, S. R.; Cortis, C; Shenkin, P. S.; Friesner, R. A. J. Phys. Chem. B 1997, 101, 1190–1197.CrossRefGoogle Scholar
  35. 35.
    Born, M. Z. Physik 1920, 1, 45-48.CrossRefGoogle Scholar
  36. 36.
    Hirata, F.; Rejfern, P.; Levy, R. J. Quantum Chem. 1988, 15, 179–188.CrossRefGoogle Scholar
  37. 37.
    Still, W. C; Tempczyk, A.; Hawley, R. C; Hendrickson, T. J. Am. Chem. Soc. 1990, 112, 6127–6129.CrossRefGoogle Scholar
  38. 38.
    Jean-Charles, A.; Nichols, A.; Sharp, K.; Honing, B.; Tempczyk, A.; Hendrickson, T. F.; Still, W. C. J. Am. Chem. Soc. 1991, 113, 1454–1455.CrossRefGoogle Scholar
  39. 39.
    Qiu, D.; Shenkin, P. S.; Hollinger, F. P.; Still, W. C. J. Phys. Chem. A 1997, 101, 3005–3014.CrossRefGoogle Scholar
  40. 40.
    Ghosh, A.; Rapp, C. S.; Friesner, R. A. J. Phys. Chem. B 1998, 102, 10983–10990.CrossRefGoogle Scholar
  41. 41.
    Roux, B.; Simonson, T. Biophysical Chemistry 1999, 78, 1–20.PubMedCrossRefGoogle Scholar
  42. 42.
    Zhang, L.; Gallicchio, E.; Friesner, R.; Levy, R. M. J. Comp. Chem. 2001, 22, 591–607.CrossRefGoogle Scholar
  43. 43.
    Novotny, J.; Bruccoleri, R.; Karplus, M. J. Mol. Biol 1984, 177, 787–818.PubMedCrossRefGoogle Scholar
  44. 44.
    Novotny, J.; Rashin, A. A.; Bruccoleri, R. Proteins: Struct. Fund. Genet. 1988, 4, 19–30.CrossRefGoogle Scholar
  45. 45.
    Chiche, L.; Gregoret, L. M.; Cohen, F. E.; Kollman, P. A. Proc. Natl. Acad. Sci. USA 1990, 87, 3240–3243.PubMedCrossRefGoogle Scholar
  46. 46.
    Vila, J.; Williams, R. L.; Vasquez, M.; Scheraga, H. A. Proteins: Struct. Fund. Genet. 1991, 10, 199–218.CrossRefGoogle Scholar
  47. 47.
    Williams, R. L.; Vila, J.; Perrot, G.; Scheraga, H. A. Proteins: Struct. Fund. Genet. 1992, 14, 110–119.CrossRefGoogle Scholar
  48. 48.
    Wang, Y.; Zhang, H.; Li, W.; Scott, R. A. Proc. Nat. Acad. Sci. (USA) 1995, 92, 709–713.CrossRefGoogle Scholar
  49. 49.
    Wang, Y.; Zhang, H.; Scott, R. A. Protein Sci. 1995, 4, 1402–1411.PubMedCrossRefGoogle Scholar
  50. 50.
    Vieth, M.; Kolinski, A.; Ill, C. L. B.; Skolnick, J. J. Mol. Biol. 1994, 237, 361–367.PubMedCrossRefGoogle Scholar
  51. 51.
    Weiner, S. J.; Kollman, P. A.; Case, D. A.; Singh, U. C; Ghio, C; Alagone, G.; Profeta, S.; Weiner, P. J. Am. Chem. Soc. 1984, 106, 765–784.CrossRefGoogle Scholar
  52. 52.
    Vorobjev, Y. N.; Almagro, J. C; Hermans, J. Proteins: Struct. Fund. Genet. 1998, 32, 399–413.CrossRefGoogle Scholar
  53. 53.
    Dominy, B.; Brooks III, C. manuscript, 2001.Google Scholar
  54. 54.
    Park, B.; Levitt, M. J. Mol. Biol. 1996, 258, 367–392.PubMedCrossRefGoogle Scholar
  55. 55.
    Hendlich, M.; Lackner, P.; Weitckus, S.; Floeckner, EL; Froschauer, R.; Gottsbacher, K.; Casari, G.; Sippl, M. J. J. Mol. Biol. 1990, 216, 167–180.PubMedCrossRefGoogle Scholar
  56. 56.
    Sippl, M. J. Curr. Opin. Struct. Biol. 1995, 5, 229-235.PubMedCrossRefGoogle Scholar
  57. 57.
    Jernigan, R. L.; Bahar, I. Curr. Opin. Struct. Biol. 1996, 6, 195–209.PubMedCrossRefGoogle Scholar
  58. 58.
    Miyazawa, S.; Jernigan, R. J. J. Mol. Biol. 1996, 256, 623–644.PubMedCrossRefGoogle Scholar
  59. 59.
    Wallqvist, A.; Smythers, G. W.; Covell, D. G. Protein Sci. 1997, 6, 1627–1642.PubMedCrossRefGoogle Scholar
  60. 60.
    Miyazawa, S.; Jernigan, R. L. Proteins: Struct. Fund. Genet. 1999, 36, 357–369.CrossRefGoogle Scholar
  61. 61.
    Covell, D.; Jernigan, R. Biochemistry 1990, 29, 3287–3294.PubMedCrossRefGoogle Scholar
  62. 62.
    Ozkan, B.; Bahar, I. Proteins: Struct. Fund. Genet. 1998, 32, 211–222.CrossRefGoogle Scholar
  63. 63.
    Samudrala, R.; Moult, J. J. Mol. Biol. 1998, 275, 895–916.PubMedCrossRefGoogle Scholar
  64. 64.
    Simons, K. T.; Ruczinski, I.; Kooperberg, C; Fox, B. A.; Bystroff, C; Baker, D. Proteins: Struct. Fund. Genet. 1999, 34, 82–95.CrossRefGoogle Scholar
  65. 65.
    Jorgensen, W. L.; Maxwell, D. S.; Tirado-Rives, J. J. Am. Chem. Soc. 1996, 118, 11225-11236.CrossRefGoogle Scholar
  66. 66.
    Huang, E. S.; Subbiah, S.; Tsai, J.; Levitt, M. J. Mol. Biol. 1996, 257, 716–725.PubMedCrossRefGoogle Scholar
  67. 67.
    Park, B. H.; Huang, E. S.; Levitt, M. J. Mol. Biol. 1997, 266, 831–846.PubMedCrossRefGoogle Scholar
  68. 68.
    Kitchen, D. B.; Hirata, F.; Westbrook, J. D.; Levy, R.; Korke, D.; Yarmush, M. J. Comp. Chem. 1990, 11, 1169–1180.CrossRefGoogle Scholar
  69. 69.
    Abola, E. E.; Bernstein, F. C; Bryant, S. H.; Koetzle, T. F.; Weng, J. Protein Data Bank. In Crystallographic Databases - Information Content, Software Systems, Scientific Applications; Allen, F. H.; Bergerhoff, G.; Sievers, R., Eds.; Data Commission of the International Union of Crystallography, Bonn/Cambridge/Chester: 1987.Google Scholar
  70. 70.
    Zhang, L.; Gallicchio, E.; Levy, R. M. Implicit solvent models for protein-ligand binding: Insights based on explicit solvent simulations. In Simulation and theory of electrostatic interactions in solution. AIP conference proceedings 492; Pratt, L. R.; Hummer, G., Eds.; American Institute of Physics: 1999.Google Scholar
  71. 71.
    ProCeryon — A software package for fold recognition and protein structure analysis, ProCeryon Biosciences; 1999–2000.Google Scholar
  72. 72.
    Levitt, M. J. Mol Biol 1992, 226, 507–533.PubMedCrossRefGoogle Scholar
  73. 73.
    Press, W. H.; Teukolsky, S. A.; Vetterling, W. T.; Flannery, B. P. Numerical Recipes in FORTRAN: The Art of Scientific Computing; Press Syndicate of the University of Cambridge: Cambridge, second ed.; 1992.Google Scholar
  74. 74.
    Sippl, M. J. Mol Biol 1990, 213, 859–883.PubMedCrossRefGoogle Scholar
  75. 75.
    Sippl, M. J. Comput. Aided Mol Design 1993, 7, 473–501.CrossRefGoogle Scholar
  76. 76.
    Dill, K. A. Biochemistry 1990, 29, 7133–7155.PubMedCrossRefGoogle Scholar
  77. 77.
    Dill, K. A. Curr. Opin. Struct. Biol. 1993, 3, 99–103.CrossRefGoogle Scholar
  78. 78.
    Schaefer, M.; Bartels, C; Karplus, M. Theoretical Chemistry Accounts 1998, 101, 194–204.CrossRefGoogle Scholar
  79. 79.
    Lazarids, T.; Karplus, M. Proteins: Struct. Fund. Genet. 1999, 35, 133–152.CrossRefGoogle Scholar
  80. 80.
    Petrey, D.; Honig, B. Protein Sci. 2000, 9, 2181–2191.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • Anthony K. Felts
    • 1
  • Anders Wallqvist
    • 1
  • Emilio Gallicchio
    • 1
  • Donna Bassolino
    • 2
  • Stanley R. Krystek
    • 2
  • Ronald M. Levy
    • 1
  1. 1.Department of ChemistryRutgers University, Wright-Rieman LaboratoriesPiscatawayUSA
  2. 2.Bristol-Myers SquibbPharmaceutical Research InstitutePrincetonUSA

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