Differential Behavior of Conformational Dynamics in Active and Inactive States of Cannabinoid Receptor 1.

ABSTRACT: Cannabinoid receptor 1 (CB1) is a G protein-coupled receptor that regulates critical physiological processes including pain, appetite, and cognition. Understanding the conformational dynamics of CB1 associated with transitions between inactive and active signaling states is imperative for developing targeted modulators. Using microsecond-level all-atom molecular dynamics simulations, we identified marked differences in the conformational ensembles of inactive and active CB1 in apo. The inactive state exhibited substantially increased structural heterogeneity and plasticity compared to the more rigidified active state in the absence of stabilizing ligands. Transmembrane helices TM3 and TM7 were identified as distinguishing factors modulating the state-dependent dynamics. TM7 displaye

SUBMITTER: Isu UH 

PROVIDER: S-EPMC11382280 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature