Impact of distal mutations on the network of coupled motions correlated to hydride transfer in dihydrofolate reductase.

ABSTRACT: A comprehensive analysis of the network of coupled motions correlated to hydride transfer in dihydrofolate reductase is presented. Hybrid quantum/classical molecular dynamics simulations are combined with a rank correlation analysis method to extract thermally averaged properties that vary along the collective reaction coordinate according to a prescribed target model. Coupled motions correlated to hydride transfer are identified throughout the enzyme. Calculations for wild-type dihydrofolate reductase and a triple mutant, along with the associated single and double mutants, indicate that each enzyme system samples a unique distribution of coupled motions correlated to hydride transfer. These coupled motions provide an explanation for the experimentally measured nonadditivity effects in th

SUBMITTER: Wong KF 

PROVIDER: S-EPMC1100751 | biostudies-literature | 2005 May

REPOSITORIES: biostudies-literature