Dynamic recognition of naloxone, morphine and endomorphin1 in the same pocket of µ-opioid receptors.

ABSTRACT: Morphine, the most widely used analgesic, relieves severe pain by activating the μ-opioid receptor (MOR), whereas naloxone, with only slight structural changes compared to morphine, exhibits inhibitory effect, and is used to treat opioid abuse. The mechanism by which the MOR distinguishes between the two is unclear. Molecular dynamics (MD) simulations on a 1-μs time scale and metadynamics-enhanced conformational sampling are used here to determine the different interactions of these two ligands with MOR: morphine adjusted its pose by continuously flipping deeper into the pocket, whereas naloxone failed to penetrate deeper because its allyl group conflicts with several residues of MOR. The endogenous peptide ligand endomorphin-1 (EM-1) underwent almost no significant conformational changes

SUBMITTER: Zhang X 

PROVIDER: S-EPMC9424762 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature