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Molecular Mechanics and Dynamics Simulations of Enzymes

  • Chapter
Computational Approaches to Biochemical Reactivity

Part of the book series: Understanding Chemical Reactivity ((UCRE,volume 19))

Conclusions

Since the first work describing a molecular dynamics simulation of a small protein was published (McCammon et al. 1977), there has been explosive growth in research concerned with theoretical studies of proteins and enzymes (McCammon and Harvey 1987; Brooks, et al 1988; Warshel 1991). Most of the studies have used empirical energy functions. This chapter describes the nature of the empirical energy function, its use in molecular mechanics calculations and molecular dynamics simulations and presents several applications to enzymes. Most important is the result that starting with x-ray structures of unproductive and static complexes of the enzyme formed with pseudosubstrates and inhibitors, simulations of the enzyme complexed with true substrates can provide direct information on the positions and dynamics of catalytically important residues. This makes it possible to explore the contribution of various amino acids to the enzyme reaction, even without a complete calculation of the reaction path. The latter requires extended potential surfaces of the QM/MM type that include bond rupture and bond formation.

Large scale conformational changes play an important role in enzyme function; several examples are reviewed in this chapter. Molecular mechanics calculations, in particular, energy minimization and normal mode calculations, as well as molecular dynamics simulations have been employed to provide an understanding of the mechanisms of such motions and their role in the enzyme.

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Authors and Affiliations

  1. Laboratire de Chimie Biophysique, URA 422 CNRS Institute Le Bel, Université Louis Pasteur, 67000, Strasbourg, France

    Roland H. Stote, Annick Dejaegere & Martin Karplus

  2. Ecole Supérieure de Biotechnologie de Strasbourg, CNRS-UPR 9003, Bd Sébastien Brant, 67400, Illkirch-Graffenstaden, France

    Annick Dejaegere

  3. Department of Chemistry, Harvard University, 12 Oxford Street, Cambridge, MA, 02138, USA

    Martin Karplus

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  1. Roland H. Stote
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  1. Department of Theoretical Chemistry, Eötvös Loránd University, Budapest, Hungary

    Gábor Náray-Szabó

  2. Department of Chemistry, University of Southern California, Los Angeles, California, USA

    Arieh Warshel

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Stote, R.H., Dejaegere, A., Karplus, M. (2002). Molecular Mechanics and Dynamics Simulations of Enzymes. In: Náray-Szabó, G., Warshel, A. (eds) Computational Approaches to Biochemical Reactivity. Understanding Chemical Reactivity, vol 19. Springer, Dordrecht. https://doi.org/10.1007/0-306-46934-0_4

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