Delineating the Ligand–Receptor Interactions That Lead to Biased Signaling at the μ-Opioid Receptor
Brendan Kelly, Scott A. Hollingsworth, David C. Blakemore, Robert M. Owen, Richard Storer, Nigel A. Swain, Deniz Aydın, Rubben Torella, Joseph S. Warmus, Ron O. Dror
Abstract
enantiomers adopt different poses that form distinct interactions with the binding pocket. A handful of specific interactions with highly conserved binding pocket residues appear to be responsible for substantial differences in arrestin recruitment between enantiomers. Our results offer guidance for rational design of biased agonists at μOR and possibly at related GPCRs.
Topics & Concepts
G protein-coupled receptorFunctional selectivityArrestinChemistryReceptorEnantiomerRational designComputational biologyLigand (biochemistry)Opioid receptorG proteinSignal transductionPharmacologyOpioidBiologyStereochemistryBiochemistryGeneticsReceptor Mechanisms and SignalingNeuropeptides and Animal PhysiologyComputational Drug Discovery Methods