Dynamic allosteric networks drive adenosine A₁ receptor activation and G-protein coupling.

ABSTRACT: G-protein coupled receptors (GPCRs) present specific activation pathways and signaling among receptor subtypes. Hence, an extensive knowledge of the structural dynamics of the receptor is critical for the development of therapeutics. Here, we target the adenosine A₁ receptor (A₁R), for which a negligible number of drugs have been approved. We combine molecular dynamics simulations, enhanced sampling techniques, network theory and pocket detection to decipher the activation pathway of A₁R, decode the allosteric networks and identify transient pockets. The A₁R activation pathway reveal hidden intermediate and pre-active states together with the inactive and fully-active states observed experimentally. The protein energy networks computed throughout

SUBMITTER: Maria-Solano MA 

PROVIDER: S-EPMC10473838 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature