Predicting novel binding modes of agonists to β adrenergic receptors using all-atom molecular dynamics simulations.

ABSTRACT: Understanding the binding mode of agonists to adrenergic receptors is crucial to enabling improved rational design of new therapeutic agents. However, so far the high conformational flexibility of G protein-coupled receptors has been an obstacle to obtaining structural information on agonist binding at atomic resolution. In this study, we report microsecond classical molecular dynamics simulations of β(1) and β(2) adrenergic receptors bound to the full agonist isoprenaline and in their unliganded form. These simulations show a novel agonist binding mode that differs from the one found for antagonists in the crystal structures and from the docking poses reported by in silico docking studies performed on rigid receptors. Internal water molecules contribute to the stabilization of novel inter

SUBMITTER: Vanni S 

PROVIDER: S-EPMC3017103 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature