Journal of Biosciences

, Volume 8, Issue 1–2, pp 167–178 | Cite as

Free energy simulations: Applications to the study of liquid water, hydrophobic interactions and solvent effects on conformational stability

  • D. L. Beveridge
  • M. Mezei
  • G. Ravishanker
  • B. Jayaram


Free energy simulations using the Metropolis Monte Carlo method and the coupling parameter approach with umbrella sampling are described for several problems of interest in structural biochemistry; the liquid water, the hydrophobic interaction of alkyl and phenyl groups in water and solvent effects on the conformational stability of the alanine dipeptide and the dimethyl phosphate anion in water. Proximity analysis of results is employed to identify stabilizing factors. Implications of result with respect to the structural chemistry of proteins and nucleic acids is considered.


Free energy simulations hydrophobic interactions solvent effects in conformation 


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  1. Adams, D. J. (1975)Mol. Phys.,29, 311.CrossRefGoogle Scholar
  2. Avignon, M., Garrigou-Lagrange, C. and Bothorel, P. (1973)Biopolymers,12, 1651.CrossRefGoogle Scholar
  3. Avignon, M. and Lascombe, J. (1973)Conformation of Biological Molecules and Polymers (eds E. Bergman and B. Pullman) (New York: Academic Press).Google Scholar
  4. Berendsen, H. C. (1984)Proceedings of a workshop on Molecular Dynamics and Structure (eds J. Hermans and W. Van Gunsteren) (Chapel Hill, N. C.).Google Scholar
  5. Berens, P. H., Mackay, D. H. J., White, G. M. and Wilson, K. R. (1983)J. Chem. Phys.,79, 3375.CrossRefGoogle Scholar
  6. Berkovitz, M., Karlin, J. A., McCammon, A. and Rossky, P. J. (1984)Chem. Phys. Lett.,105, 577.CrossRefGoogle Scholar
  7. Berman, H. M. and Sheng, H. S. (1981)Topics in Nucleic Acid Structures, PartI, (ed. S. Neidle).Google Scholar
  8. Beveridge, D. C., Maye, P. V., Jayaram, B., Ravishanker, G. and Mezei, M. (1984)J. Biomol. Struct. Dyn.,2, 261.CrossRefGoogle Scholar
  9. Beveridge, D. L. and Mezei, M. (1985)Proc. of a Workshop on Molecular Dynamics and Protein Structure (eds J. Hermans and W. van Gunsteren) (Chapel Hill).Google Scholar
  10. Beveridge, D. L., Mezei, M., Mehrotra, P. K., Marchese, F. T., Ravishanker, G., Vasu, T. R., and Swaminathan, S. (1983)Molecular based study and prediction of fluid properties (eds J. M. Haile and G. Mansoori) (Advances in chemistry series, American Chemical Society) Vol.204.Google Scholar
  11. Beveridge, D. L., Mezei, M., Mehrotra, P. K., Marchese, F. T., Thirumalai, V. and Ravishanker, G. 1981Ann. N. Y. Acad. Sci.,367, 108.CrossRefGoogle Scholar
  12. Chandrasekhar, J., Smith, F. S. and Jorgensen, W. L. (1984)J. Am. Chem. Soc.,106, 3049.CrossRefGoogle Scholar
  13. Chandrasekhar, J., Smith, F. S. and Jorgensen, W. L. (1985)J. Am. Chem. Soc.,107, 154.CrossRefGoogle Scholar
  14. Clark, A. H., Franks, F., Pedley, M. D. and Reid, D. S. (1977)J. Chem. Soc. Faraday Trans. I,73, 290.CrossRefGoogle Scholar
  15. Clementi, E. (1980)Computational aspect for large chemical systems (New York: Springer Verlag).CrossRefGoogle Scholar
  16. Corongiu, G., Clementi, E. (1981)Gazz. Chim. Ital.,108, 273.Google Scholar
  17. Finney, J. L, Goodfellow, J. M., Howell, P. L. and Vovelle, F. (1985)J. Biomol. Struct. and Dyn., (in press). (in press).Google Scholar
  18. Franks, F. (1975)Water-A Comprehensive Treatise (ed. F. Franks) (New York: Plenum Press) Vol. 4, Chapter 1.CrossRefGoogle Scholar
  19. Franks, F. (1977)J. Chem. Soc. Faraday Trans. I, 73, 830.CrossRefGoogle Scholar
  20. Franks, F. and Ives, D. G. J. (1966)Quart. Rev. Chem. Soc.,20, 1.CrossRefGoogle Scholar
  21. Gorenstein, D. G., Luxton, B. A. and Findlay, J. B. (1977)Biochim. Biophys. Acta,475, 184.CrossRefGoogle Scholar
  22. Jacucci, G. and Quirke, N. (1982)Mol. Phys.,40, 1005.CrossRefGoogle Scholar
  23. Jorgensen, W. L. (1982)J. Chem. Phys.,77, 5757.CrossRefGoogle Scholar
  24. Jorgensen, W. L. (1983)J. Phys. Chem.,87, 5304.CrossRefGoogle Scholar
  25. Kirkwood, J. G. (1968)Theory of Liquids, (ed. B. J. Alder) (New York: Gordon and Breach).Google Scholar
  26. Madison, V. and Kopple, K. D. (1980)J. Am. Chem. Soc.,102, 4855.CrossRefGoogle Scholar
  27. Mehrotra, P. K. and Beveridge, D. L. (1980)J. Am. Chem. Soc.,102, 4287.CrossRefGoogle Scholar
  28. Mehrotra, P. K., Mezei, M. and Beveridge, D. L. (1983)J. Chem. Phys.,78, 3156.CrossRefGoogle Scholar
  29. Mehrotra, P. K., Mezei, M. and Beveridge, D. L. (1984)Int. J.Quantum Chem.: Quantum Biol. Symp.,11, 301.CrossRefGoogle Scholar
  30. Metropolis, N., Rosenbluth, A. W., Rosenbluth, M. N., Teller, A. H. and Teller, E. (1953)J.Chem. Phys.,21, 2087.CrossRefGoogle Scholar
  31. Mezei, M. (1982)Mol. Phys.,47, 1307.CrossRefGoogle Scholar
  32. Mezei, M., Mehrotra, P. K. and Beveridge, D. L. (1985)J. Am. Chem. Soc.,107, 2239.CrossRefGoogle Scholar
  33. Mezei, M., Swaminathan, S. and Beveridge, D. L. (1978)J. Am. Chem. Soc.,100, 3255.CrossRefGoogle Scholar
  34. Miyazaki, M., Barker, J. A. and Pound, G. M. (1976)J. Chem. Phys.,64, 3364.CrossRefGoogle Scholar
  35. Mruzik, M. R., Abraham, F. F., Schreiber, D. E. and Pound, G. M. (1976)J. Chem. Phys.,64, 481.CrossRefGoogle Scholar
  36. Norman, G. E. and Filinov, V. S. (1969)High Temp. USSR,7, 216.Google Scholar
  37. Olson, W. K. (1982)Topics in Nucleic Acid Structures: Part 2 (ed. S. Neidle).Google Scholar
  38. Owicki, J. and Scheraga, H. A. (1977)J. Am. Chem. Soc.,99, 8382.Google Scholar
  39. Owicki, J. and Scheraga, H. A. (1978)J. Phys. Chem.,82, 1257.CrossRefGoogle Scholar
  40. Pangali, C, Rao, M. and Berne, B. J. (1979a)J. Chem. Phys.,71, 2975.CrossRefGoogle Scholar
  41. Pangali, C, Rao, M. and Berne, B. J. (1979b)J. Chem. Phys.,71, 2982.CrossRefGoogle Scholar
  42. Patey, G. N. and Valleau, J. P. (1975)J Chem. Phys.,63, 2334.CrossRefGoogle Scholar
  43. Postma, J. P. M., Berendsen, H. J. C. and Haak, J. R. (1982)Faraday Symp. Chem. Soc.,82, 55.CrossRefGoogle Scholar
  44. Powles, J. G., Evans, W. A. B. and Quirke, N. (1982)Mol. Phys.,46, 1347.CrossRefGoogle Scholar
  45. Pratt, L. and Chandler, D. (1977)J. Chem. Phys.,67, 3683.CrossRefGoogle Scholar
  46. Quirke, N. and Jacucci, G. (1982)Mol. Phys.,45, 823.CrossRefGoogle Scholar
  47. Ravishanker, G. and Beveridge, D. L. (1985)J. Am. Chem. Soc.,107, 2565.CrossRefGoogle Scholar
  48. Ravishanker, G., Mezei, M. and Beveridge, D. L. (1982)Symp. Faraday Soc.,17, 79.CrossRefGoogle Scholar
  49. Rebertus, D. W., Berne, B. J. and Chandler, D. (1979)J. Chem. Phys.,75, 3395.CrossRefGoogle Scholar
  50. Romano, S. and Singer, K. (1979)Mol. Phys.,37, 1765.CrossRefGoogle Scholar
  51. Sarkisov, G. N., Dashevsky, V. G. and Malenkov, G. G. (1974)Mol. Phys.,27, 1249.CrossRefGoogle Scholar
  52. Scott, H. L. and Lee, C. Y. (1980)J. Chem. Phys.,73, 4591.CrossRefGoogle Scholar
  53. Shing, K. S. and Gubbins, K. E., (1981)Mol. Phys.,43, 717.CrossRefGoogle Scholar
  54. Shing, K. S. and Gubbins, K. E. (1982)Mol. Phys.,46, 1109.CrossRefGoogle Scholar
  55. Swope, W. C., Andersen, H. C., Berens, P. H. and Wilson, K. R. (1982)J. Chem. Phys.,76, 637.CrossRefGoogle Scholar
  56. Torrie, G. and Valleau, J. P. (1977)J. Comp. Phys.,23, 187.CrossRefGoogle Scholar
  57. Windom, B. (1963)J. Chem. Phys.,39, 2808.CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 1985

Authors and Affiliations

  • D. L. Beveridge
    • 1
  • M. Mezei
    • 1
  • G. Ravishanker
    • 1
  • B. Jayaram
    • 1
  1. 1.Department of ChemistryHunter College of the City University of New YorkNew YorkUSA

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