How μ-Opioid Receptor Recognizes Fentanyl.

ABSTRACT: In 2019, drug overdose has claimed over 70,000 lives in the United States. More than half of the deaths are related to synthetic opioids represented by fentanyl which is a potent agonist of mu-opioid receptor (mOR). In recent years, the crystal structures of mOR in complex with morphine derivatives have been determined; however, structural basis of mOR activation by fentanyl-like synthetic opioids remains lacking. Exploiting the X-ray structure of mOR bound to a morphinan ligand and several state-of-the-art simulation techniques, including weighted ensemble and continuous constant pH molecular dynamics, we elucidated the detailed binding mechanism of fentanyl with mOR. Surprisingly, in addition to forming a salt-bridge with Asp147^3.32 in the orthosteric site common to morphinan

SUBMITTER: Vo QN 

PROVIDER: S-EPMC7444290 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature