Efficient in silico exploration of RNA interhelical conformations using Euler angles and WExplore.

ABSTRACT: HIV-1 TAR RNA is a two-helix bulge motif that plays a critical role in HIV viral replication and is an important drug target. However, efforts at designing TAR inhibitors have been challenged by its high degree of structural flexibility, which includes slow large-amplitude reorientations of its helices with respect to one another. Here, we use the recently introduced algorithm WExplore in combination with Euler angles to achieve unprecedented sampling of the TAR conformational ensemble. Our ensemble achieves similar agreement with experimental NMR data when compared with previous TAR computational studies, and is generated at a fraction of the computational cost. It clearly emerges from configuration space network analysis that the intermittent formation of the A22-U40 base pair acts as a

SUBMITTER: Dickson A 

PROVIDER: S-EPMC4231733 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature