SuperBiHelix method for predicting the pleiotropic ensemble of G-protein-coupled receptor conformations.

ABSTRACT: There is overwhelming evidence that G-protein-coupled receptors (GPCRs) exhibit several distinct low-energy conformations, each of which might favor binding to different ligands and/or lead to different downstream functions. Understanding the function of such proteins requires knowledge of the ensemble of low-energy configurations that might play a role in this pleiotropic functionality. We earlier reported the BiHelix method for efficiently sampling the (12)(7) = 35 million conformations resulting from 30° rotations about the axis (η) of all seven transmembrane helices (TMHs), showing that the experimental structure is reliably selected as the best conformation from this ensemble. However, various GPCRs differ sufficiently in the tilts of the TMHs that this method need not predict the opt

SUBMITTER: Bray JK 

PROVIDER: S-EPMC3890820 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature