Abstract
Two methods for computer simulation of enzymatic reactions are described. The first method allows one to estimate activation-free energies of enzymatic reactions by using available X-ray structures of enzyme-substrate complexes. This method is based on the empirical valence bond (EVB) approach which correlates reaction rates with the difference in electrostatic stabilization of the relevant resonance structures in the enzyme and in solution. The second method is based on a molecular dynamics extension of the EVB approach. This method allows one to study fundamental aspects of enzymatic reactions, including analysis of the role of structural fluctuations and estimates of entropic effects. The dynamical method is used here for examination of the relationship between reaction free energies (ΔGo) and activation free energies (Δg≠) in enzyme catalysis. The preliminary results presented here indicate that the rates of proton transfer reactions in enzymes might be correlated in a simple way with the corresponding pKa differences.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Allen, L. G. (1981) Ann. N.Y. Acad. Sci., 367, 383–392.
Anderson, J. B. (1973) J. Chem. Phys., 58, 4684–4692.
Bolis, G., Ragazzi, M., Salvaderi, D., Ferro, D. R. and Clementi, E. (1978) Gazzetta Chem. Ital., 108, 425–443.
Careri, G., Fasella, P. and Gratton, E. (1979) Ann. Rev. Biophys. Bioeng., 8, 69–97.
Fraunfelder, H., Petsko, G. and Tsernoglu, A. (1979) Nature, 280, 558–563.
Glasstone, S., Laidler, K. J. and Eyring, H. (1941) The Theory of Rate Processes, McGraw-Hill, New York, 153–201.
Karplus, M. and McCammon, A. J. (1981) CRC Crit. Rev. Biochem., 9, 293–349.
Keck, J. C. (1966) Adv. Chem. Phys., 13, 85–121.
Kollman, P. A. and Hayes, D. M. (1981) J. Am. Chem. Soc., 103, 2953–2961.
Levitt, M. (1981) Nature, 294, 379–380.
Lifson, S. and Warshel, A. (1968) J. Chem. Phys., 49, 5116–5124.
Loew, G. and Thomas, D. D. (1972) J. Theor. Biol., 36, 98–104.
Naray-Szabo, G., Bleha, T. (1982) Progress in Theoretical Organic Chemistry, ed. Csizmadia, I.G., Vol. 3, 267–336.
Page, M. I. and Jencks, W. P. (1971) Proc. Nat. Acad. Sci. USA, 68, 1678–1683.
Scheiner, S., Kleier, D. A. and Lipscomb, W.N. (1975) Proc. Natl. Acad. Sci. USA, 72, 2606–2610.
Scheiner, S. and Lipscomb, W. N. (1976) Proc. Natl. Acad. Sci. USA, 73, 432–436.
Tapia, O., Johanin, G. (1981) J. Chem. Phys., 75, 3624–3634.
Tully, J. G. (1981) Computers and Chemistry, 4, 159–156.
Umeyama, H., Imamura, A., Nagata, C. and Hanano, M. (1973) J. Theor. Biol., 41, 485–502.
Valleau, J. P. and Torrie, G. M. (1977) in Modern Theoretical Chemistry, ed. B. Berne, Vol. 5, Plenum Press, New York, 137–193.
Van Duijnen, P. T., Thole, B. Th. and Hol, W. G. J. (1979) Biophys. Chem., 9, 273–280.
Warshel, A. (1976) Nature, 260, 679–683.
Warshel, A. and Levitt, M. (1976) J. Mol. Biol., 103, 227–249.
Warshel, A. (1979) J. Phys. Chem., 83, 1640–1652.
Warshel, A. and Weiss, R. M. (1980) J. Am. Chem. Soc., 102, 6218–6226.
Warshel, A. (1981a) Biochemistry, 20, 3167–3177.
Warshel, A. (1981b) Acc. Chem. Res., 14, 284–290.
Warshel, A., Russell, S. and Weiss, R. M. (1982) in Chemical Approaches to Understanding Enzyme Catalysis, ed. Green, B. S., Ashani, Y. and Chipman, D., Studies in Organic Chemistry, Vol. 10, Elsevier Scientific Publishing Co., Amsterdam, 267–279.
Warshel, A. (1982) J. Phys. Chem., 86, 2218–2224.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1984 Pontificia Academia Scientiarum — Città del Vaticano
About this paper
Cite this paper
Warshel, A. (1984). Simulating the Energetics and Dynamics of Enzymatic Reactions. In: Chagas, C., Pullman, B. (eds) Specificity in Biological Interactions. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-6457-0_4
Download citation
DOI: https://doi.org/10.1007/978-94-009-6457-0_4
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-009-6459-4
Online ISBN: 978-94-009-6457-0
eBook Packages: Springer Book Archive