Microscopic Simulations of Chemical Reactions in Solutions and Protein Active Sites; Principles and Examples

  • Arieh Warshel
Part of the Progress in Mathematics book series (NSSA)


The reason for the enormous catalytic power of enzymes is one of the most fundamental questions in molecular biophysics. Disregarding magical effects it is clear that enzyme catalysis must be based on some clear and probably simple physical concepts. This paper will examine the microscopic origin of enzyme catalysis by computer simulation approaches. Methods for simulation of chemical reactions in solutions and proteins will be reviewed, emphasizing the insight obtained from the simple Empirical Valence Bond (EVB) formulation. The reader will be introduced to simple approaches that should let him judge for himself which catalytic effects are important and how to formulate a mechanistic hypothesis in terms of well defined energy values.


Proton Transfer Potential Surface Solvation Free Energy Activation Free Energy Linear Free Energy Relationship 
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  1. (1).
    Warshel, A. and Weiss, R.M. (1980). J. Am. Chem. Soc., 102, 6218–6226.Google Scholar
  2. (2).
    Coulson, C.A., and Danielsson, U. (1954). Part II. Ark. Fys., 8, 245–255.Google Scholar
  3. (3).
    Born, M. (1920) Phys. I, 45–48.Google Scholar
  4. (4).
    Kirkwood, J.G. (1934). J. Chem. Phys., 2, 351–361.Google Scholar
  5. (5).
    Warshel, A. and Russell, S. (1984) Quart. Rev. of Biophys. 17 283–427.CrossRefGoogle Scholar
  6. (6).
    Russell, S. and Warshel, A. (1985) J. Mol. Biol.Google Scholar
  7. (7).
    Hwang, J-K., King, G., Creighton, S., and Warshel, A. (1988) J. Am. Chem. Soc. (in press).Google Scholar
  8. (8).
    Valleau, J.P. and Torrie G.M. (1972) in Modern Theoretical Chemistry ed. Berne, B. (Plennum, New York) Vol 5 pp. 137Google Scholar
  9. (9).
    Warshel, A., J. Phys. Chem. (1982) 86, 2218.CrossRefGoogle Scholar
  10. (b).
    Hwang, J.-K. and Warshel A. (1987) J. Am. Chem. Soc. 109, 715.CrossRefGoogle Scholar
  11. (10).
    Marcus, R.A. (1968) J. Phys. Chem. 72, 891.Google Scholar
  12. (11).
    Bronsted, J.N. and Pederson, K. (1924) Z. Phys. Chem. 108, 185.Google Scholar
  13. (12).
    Hammond, G.S. (1955) J. Am. Chem. Soc. 77, 334.CrossRefGoogle Scholar
  14. (13).
    Albery, J.W. and Kreevoy, M.M. (1978) Adv. Phys. Org. Chem. 16, 87.Google Scholar
  15. (14).
    Warshel, A., Russell, S.T. and Sussman F. (1987) Israel J. Chem. 27, 217.CrossRefGoogle Scholar
  16. (15).
    a) Blake, C.C.F., Mair, G.A., North, A.C.T., Philips, D.C., Sarma, V.R. (1967) Proc. R. Soc. London, Ser. B, 167, 365.Google Scholar
  17. (b).
    Philips, D.C. (1966) Sci. Am. 215 78–90.Google Scholar
  18. (16).
    Warshel, A. and Levitt, M. (1976). J. Molec. Biol., 103, 227–249.Google Scholar
  19. (17).
    Dunn, B.M., Bruice, T.C., Adv. Enzymol. Relat. Areas Mol. Biol., (1973), 37, 1–59.Google Scholar
  20. (18).
    Warshel, A. (1981) Biochemistry 20, 3167.PubMedCrossRefGoogle Scholar
  21. (19).
    Blow, D.M., Birktoft, J.J., and Hartley, S.S. (1969) Nature 221, 337–340PubMedCrossRefGoogle Scholar
  22. (20).
    Kraut, J., Annu. Rev. Biochem, (1977) 46, 331–358.PubMedCrossRefGoogle Scholar
  23. (21).
    Stroud, R.M., Kossiakoff, A.A., Chambers, J.L., (1977) Ann. Rev. Biophys. Bioeng. 6, 177–193 (1977).Google Scholar
  24. (22).
    Warshel, A. and Russell, S., (1986a) J. Am. Chem. Soc. 108, 6569–6579.CrossRefGoogle Scholar
  25. (23).
    Carter, P., and Wells, J.A., Nature, (submitted).Google Scholar
  26. (24).
    Craik, C.S., Roczniak, S., Largeman, C., and Rutter, W.J., (1987) Science 237, 909–913.PubMedCrossRefGoogle Scholar
  27. (25).
    Wells, J.A., Cunningham, B.C., Craycar, T.P., and Estell, D.A. (1986) Philos. Trans. R. Soc. ( London) Ser. A No. 317, 415–423.Google Scholar
  28. (26).
    Warshel, A., and Sussman, F. (1986) Proc. Natl. Acad. Sci. (U.S.A.) 83, 3806–3810.CrossRefGoogle Scholar
  29. (27).
    Naray-Szabo, G., Sussman, F., Hwang, J-K, and Warshel, A. (submitted).Google Scholar
  30. (28).
    Cotton, F.A. Hazen, E.E., and Legg, M.J. (1979) Proc. Natl. Acad. Sci. 76 2551–2555.Google Scholar
  31. (29).
    Serpersu, E.H., Shortie, D. and Mildvan, A.S. (1987) Biochemistry, 26, 1289–1300.PubMedCrossRefGoogle Scholar
  32. (30).
    Guthrie, J.D. (1977), J. Am. Chem. Soc. 99, 3991–4001.Google Scholar
  33. (31).
    Agvist, J and Warshel, A. (1988) in preparation.Google Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Arieh Warshel
    • 1
  1. 1.Department of ChemistryUniversity of Southern CaliforniaLos AngelesUSA

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