Simulations of remote mutants of dihydrofolate reductase reveal the nature of a network of residues coupled to hydride transfer.

ABSTRACT: Recent experimental and theoretical studies have proposed that enzymes involve networks of coupled residues throughout the protein that participate in motions accompanying chemical barrier crossing. Here, we have examined portions of a proposed network in dihydrofolate reductase (DHFR) using quantum mechanics/molecular mechanics simulations. The simulations use a hybrid quantum mechanics-molecular mechanics approach with a recently developed semiempirical AM1-SRP Hamiltonian that provides accurate results for this reaction. The simulations reproduce experimentally determined catalytic rates for the wild type and distant mutants of E. coli DHFR, underscoring the accuracy of the simulation protocol. Additionally, the simulations provide detailed insight into how residues remote from the acti

SUBMITTER: Roston D 

PROVIDER: S-EPMC4082691 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature