Thumb inhibitor binding eliminates functionally important dynamics in the hepatitis C virus RNA polymerase.

ABSTRACT: Hepatitis C virus (HCV) has infected almost 200 million people worldwide, typically causing chronic liver damage and severe complications such as liver failure. Currently, there are few approved treatments for viral infection. Thus, the HCV RNA-dependent RNA polymerase (gene product NS5B) has emerged as an important target for small molecule therapeutics. Potential therapeutic agents include allosteric inhibitors that bind distal to the enzyme active site. While their mechanism of action is not conclusively known, it has been suggested that certain inhibitors prevent a conformational change in NS5B that is crucial for RNA replication. To gain insight into the molecular origin of long-range allosteric inhibition of NS5B, we employed molecular dynamics simulations of the enzyme with and with

SUBMITTER: Davis BC 

PROVIDER: S-EPMC3943204 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature