Mechanistic Insights into Specific G Protein Interactions with Adenosine Receptors.

ABSTRACT: Coupling between G-protein-coupled receptors (GPCRs) and the G proteins is a key step in cellular signaling. Despite extensive experimental and computational studies, the mechanism of specific GPCR-G protein coupling remains poorly understood. This has greatly hindered effective drug design of GPCRs that are primary targets of ∼¹/₃ of currently marketed drugs. Here, we have employed all-atom simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method to decipher the mechanism of the GPCR-G protein interactions. Adenosine receptors (ARs) were used as model systems based on very recently determined cryo-EM structures of the A₁AR and A_2AAR coupled with the G_i and G_s proteins, respectively. Changing the G

SUBMITTER: Wang J 

PROVIDER: S-EPMC7026936 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature