Hybrid quantum/classical molecular dynamics simulations of the proton transfer reactions catalyzed by ketosteroid isomerase: analysis of hydrogen bonding, conformational motions, and electrostatics.

ABSTRACT: Hybrid quantum/classical molecular dynamics simulations of the two proton transfer reactions catalyzed by ketosteroid isomerase are presented. The potential energy surfaces for the proton transfer reactions are described with the empirical valence bond method. Nuclear quantum effects of the transferring hydrogen increase the rates by a factor of approximately 8, and dynamical barrier recrossings decrease the rates by a factor of 3-4. For both proton transfer reactions, the donor-acceptor distance decreases substantially at the transition state. The carboxylate group of the Asp38 side chain, which serves as the proton acceptor and donor in the first and second steps, respectively, rotates significantly between the two proton transfer reactions. The hydrogen-bonding interactions within the a

SUBMITTER: Chakravorty DK 

PROVIDER: S-EPMC2783618 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature