Computation of kinetic isotope effects for enzymatic reactions.

ABSTRACT: We describe a computational approach, incorporating quantum mechanics into enzyme kinetics modeling with a special emphasis on computation of kinetic isotope effects. Two aspects are highlighted: (1) the potential energy surface is represented by a combined quantum mechanical and molecular mechanical (QM/MM) potential in which the bond forming and breaking processes are modeled by electronic structure theory, and (2) a free energy perturbation method in path integral simulation is used to determine both kinetic isotope effects (KIEs). In this approach, which is called the PI-FEP/UM method, a light (heavy) isotope is mutated into a heavy (light) counterpart in centroid path integral simulations. The method is illustrated in the study of primary and secondary KIEs in two enzyme systems. In t

SUBMITTER: Gao J 

PROVIDER: S-EPMC3749886 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature