Structural and energetic analysis of 2-aminobenzimidazole inhibitors in complex with the hepatitis C virus IRES RNA using molecular dynamics simulations.

ABSTRACT: Despite the many biological functions of RNA, very few drugs have been designed or found to target RNA. Here we report the results of molecular dynamics (MD) simulations and binding energy analyses on hepatitis C virus internal ribosome entry site (IRES) RNA in complex with highly charged 2-aminobenzimidazole inhibitors. Initial coordinates were taken from NMR and crystallography studies that had yielded different binding modes. During MD simulations, the RNA-inhibitor complex is stable in the crystal conformation but not in the NMR conformation. Additionally, we found that existing and standard MD trajectory postprocessing free energy methods, such as the MM-GBSA and MM-PBSA approaches available in AMBER, seem unsuitable to properly rank the binding energies of complexes between highly ch

SUBMITTER: Henriksen NM 

PROVIDER: S-EPMC4076022 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature