Insight into the Inhibitory Mechanism of Aryl Formyl Piperidine Derivatives on Monoacylglycerol Lipase through Molecular Dynamics Simulations.

ABSTRACT: Monoacylglycerol lipase (MAGL) can regulate the endocannabinoid system and thus becomes a target of antidepressant drugs. In this paper, molecular docking and molecular dynamics simulations, combined with binding free energy calculation, were employed to investigate the inhibitory mechanism and binding modes of four aryl formyl piperidine derivative inhibitors with different 1-substituents to MAGL. The results showed that in the four systems, the main four regions where the enzyme bound to the inhibitor included around the head aromatic ring, the head carbonyl oxygen, the tail amide bond, and the tail benzene ring. The significant conformational changes in the more flexible lid domain of the enzyme were caused by 1-substituted group differences of inhibitors and resulted in different degre

SUBMITTER: Liu C 

PROVIDER: S-EPMC9655140 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature