Molecular Basis of Inhibitory Mechanism of Naltrexone and Its Metabolites through Structural and Energetic Analyses.

ABSTRACT: Naltrexone is a potent opioid antagonist with good blood-brain barrier permeability, targeting different endogenous opioid receptors, particularly the mu-opioid receptor (MOR). Therefore, it represents a promising candidate for drug development against drug addiction. However, the details of the molecular interactions of naltrexone and its derivatives with MOR are not fully understood, hindering ligand-based drug discovery. In the present study, taking advantage of the high-resolution X-ray crystal structure of the murine MOR (mMOR), we constructed a homology model of the human MOR (hMOR). A solvated phospholipid bilayer was built around the hMOR and submitted to microsecond (µs) molecular dynamics (MD) simulations to obtain an optimized hMOR model. Naltrexone and its derivatives were dock

SUBMITTER: Bello M 

PROVIDER: S-EPMC9369988 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature