Enzyme Dynamics and Catalysis: Insights from Simulations

Abstract

AbstractMolecular modelling and simulation are making increasingly important contributions to the study of the structure and function of biological macromolecules. An area of particular current interest and debate is that of enzyme catalysis, and the role of protein dynamics in enzyme-catalysed reactions. Simulations allow enzyme catalytic mechanisms and protein dynamics to be investigated at the atomic level (e.g. with combined quantum mechanics/molecular mechanics (QM/MM) calculations and atomistic molecular dynamics simulations). This level of detailed analysis is beyond what is currently possible in experiments for reactions in enzymes, and simulations therefore have a crucial role to play in testing hypotheses and aiding in the interpretation of experimental data. Biomolecular simulations will therefore be crucial in resolving current controversies about the role of protein dynamics in enzyme catalysis. In this chapter we describe some recent simulations which have contributed to an understanding of enzyme mechanism, dynamics and function.KeywordsQuantum mechanicsMolecular mechanicsQMMMNAMDBiomolecular simulationMolecular modellingMolecular dynamicsConformational changesFunctional dynamicsComputational enzymology