Enzymatic Kinetic Isotope Effects from First-Principles Path Sampling Calculations.

ABSTRACT: In this study, we develop and test a method to determine the rate of particle transfer and kinetic isotope effects in enzymatic reactions, specifically yeast alcohol dehydrogenase (YADH), from first-principles. Transition path sampling (TPS) and normal mode centroid dynamics (CMD) are used to simulate these enzymatic reactions without knowledge of their reaction coordinates and with the inclusion of quantum effects, such as zero-point energy and tunneling, on the transferring particle. Though previous studies have used TPS to calculate reaction rate constants in various model and real systems, it has not been applied to a system as large as YADH. The calculated primary H/D kinetic isotope effect agrees with previously reported experimental results, within experimental error. The kinetic is

SUBMITTER: Varga MJ 

PROVIDER: S-EPMC4829465 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature