Chapter 2: Fundamentals of Enzyme Catalysis: Determination of Rate Constants

The chapter introduces or recalls the main ideas of enzyme kinetics in very brief form. The main elements of a theoretical determination by a QM/MM simulation of rate constants for an enzyme-catalysed reaction are enumerated and discussed and illustrated briefly by examples from the literature. These elements are (i) the structural, kinetic and mechanistic background information available for the reaction to be considered; (ii) the choice of the atoms to constitute the QM region of the system, the choice of QM methods to be used for this region, and the choice of methods to embed the QM region appropriately within the remaining MM region of the total system; (iii) the methods by which the potential-energy surface is to be established and the extrema (minima and saddle points) are to be located, the determination of the minimum energy swath and derivatives; (iv) the establishment of a free-energy surface, and the collection and analysis of simulations; (v) the calculation of rate constants.