Artificial reaction coordinate "tunneling" in free-energy calculations: the catalytic reaction of RNase H.

ABSTRACT: We describe a method for the systematic improvement of reaction coordinates in quantum mechanical/molecular mechanical (QM/MM) calculations of reaction free-energy profiles. In umbrella-sampling free-energy calculations, a biasing potential acting on a chosen reaction coordinate is used to sample the system in reactant, product, and transition states. Sharp, nearly discontinuous changes along the resulting reaction path are used to identify coordinates that are relevant for the reaction but not properly sampled. These degrees of freedom are then included in an extended reaction coordinate. The general formalism is illustrated for the catalytic cleavage of the RNA backbone of an RNA/DNA hybrid duplex by the RNase H enzyme of Bacillus halodurans. We find that in the initial attack of the pho

SUBMITTER: Rosta E 

PROVIDER: S-EPMC3098573 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature