Exploring the Ligand Efficacy of Cannabinoid Receptor 1 (CB1) using Molecular Dynamics Simulations.

ABSTRACT: Cannabinoid receptor 1 (CB1) is a promising therapeutic target for a variety of disorders. Distinct efficacy profiles showed different therapeutic effects on CB1 dependent on three classes of ligands: agonists, antagonists, and inverse agonists. To discriminate the distinct efficacy profiles of the ligands, we carried out molecular dynamics (MD) simulations to identify the dynamic behaviors of inactive and active conformations of CB1 structures with the ligands. In addition, the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method was applied to analyze the binding free energy decompositions of the CB1-ligand complexes. With these two methods, we found the possibility that the three classes of ligands can be discriminated. Our findings shed light on the understanding of diff

SUBMITTER: Jung SW 

PROVIDER: S-EPMC6137198 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature