Probing biased activation of mu-opioid receptor by the biased agonist PZM21 using all atom molecular dynamics simulation.

Morphine is a commonly used opioid drug to treat acute pain by binding to the mu-opioid receptor (MOR), but its effective analgesic efficacy via triggering of the heterotrimeric G protein pathway is accompanied by a series of adverse side effects via triggering of the β-arrestin pathway. Recently, PZM21, a recently developed MOR biased agonist, shows preferentially activating the G protein pathway over β-arrestin pathway. However, there is no high-resolution receptor structure in complex with PZM21 and its action mechanism remains elusive.