The full activation mechanism of the adenosine A₁ receptor revealed by GaMD and Su-GaMD simulations.

ABSTRACT: The full activation process of G protein-coupled receptor (GPCR) plays an important role in cellular signal transduction. However, it remains challenging to simulate the whole process in which the GPCR is recognized and activated by a ligand and then couples to the G protein on a reasonable simulation timescale. Here, we developed a molecular dynamics (MD) approach named supervised (Su) Gaussian accelerated MD (GaMD) by incorporating a tabu-like supervision algorithm into a standard GaMD simulation. By using this Su-GaMD method, from the active and inactive structure of adenosine A₁ receptor (A₁R), we successfully revealed the full activation mechanism of A₁R, including adenosine (Ado)-A₁R recognition, preactivation of A₁R, and A₁

SUBMITTER: Li Y 

PROVIDER: S-EPMC9586258 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature