CHAPTER 21: Molecular Dynamics Simulation of Kinetic Isotope Effects in Enzyme-Catalyzed Reactions

Quantum mechanical methods for enzyme kinetics modeling are described. Two aspects are emphasized: the use of electronic structure theory to represent the potential energy surfaces for enzyme reactions; and the incorporation of nuclear quantum effects in enzyme dynamics. These methods were illustrated by three enzymatic reactions, namely, alanine racemase, nitroalkane oxidase and dihydrofolate reductase. These examples illustrate a range of kinetic observations affected by nuclear quantum effects, ranging from the lowering of the computed free energy barrier, enhanced tunneling in enzyme catalysis, and altered temperature dependence of kinetic isotope effects.