Interaction of Synthetic Cannabinoid Receptor Agonists with Cannabinoid Receptor I: Insights into Activation Molecular Mechanism.

ABSTRACT: Synthetic cannabinoid receptor agonists (SCRAs) have become a wide group of new psychoactive substances since the 2010s. For the last few years, the X-ray structures of the complexes of cannabinoid receptor I (CB₁) with SCRAs as well as the complexes of CB₁ with its antagonist have been published. Based on those data, SCRA-CB₁ interactions are analyzed in detail, using molecular modeling and molecular dynamics simulations. The molecular mechanism of the conformational transformation of the transmembrane domain of CB₁ caused by its interaction with SCRA is studied. These conformational changes allosterically modulate the CB₁-G_i complex, providing activation of the G_i protein. Based on the X-ray-determ

SUBMITTER: Gavryushov S 

PROVIDER: S-EPMC10574015 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature