Interaction analyses of hTAAR1 and mTAAR1 with antagonist EPPTB.

Trace amine-associated receptor 1 (TAAR1) plays a critical role in regulating monoaminergic activity. EPPTB is the only known selective potent antagonist of the mouse (m) TAAR1 presently, while it was shown to be weak at antagonizing human (h) TAAR1. The lack of high-resolution structure of TAAR1 hinders the understanding of the differences in the interaction modes between EPPTB and m/hTARR1.

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.