Allosteric inhibitors have distinct effects, but also common modes of action, in the HCV polymerase.

ABSTRACT: The RNA-dependent RNA polymerase from the Hepatitis C Virus (gene product NS5B) is a validated drug target because of its critical role in genome replication. There are at least four distinct allosteric sites on the polymerase to which several small molecule inhibitors bind. In addition, numerous crystal structures have been solved with different allosteric inhibitors bound to the polymerase. However, the molecular mechanisms by which these small molecules inhibit the enzyme have not been fully elucidated. There is evidence that allosteric inhibitors alter the intrinsic motions and distribution of conformations sampled by the enzyme. In this study we use molecular dynamics simulations to understand the structural and dynamic changes that result when inhibitors are bound at three different

SUBMITTER: Davis BC 

PROVIDER: S-EPMC4390812 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature