Investigating allosteric effects on the functional dynamics of β2-adrenergic ternary complexes with enhanced-sampling simulations.

ABSTRACT: Signalling by G-protein coupled receptors usually occurs via ternary complexes formed under cooperative binding between the receptor, a ligand and an intracellular binding partner (a G-protein or β-arrestin). While a global rational for allosteric effects in ternary complexes would be of great help in designing ligands with specific effects, the paucity of structural data for ternary complexes with β-arrestin, together with the intrinsic difficulty of characterizing the dynamics involved in the allosteric coupling, have hindered the efforts to devise such a model. Here we have used enhanced-sampling atomistic molecular-dynamics simulations to investigate the dynamics and complex formation mechanisms of both β-arrestin- and G_s-complexes with the β2-adrenergic receptor (ADR

SUBMITTER: Saleh N 

PROVIDER: S-EPMC6094175 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature