title: Lessons from free energy simulations of delta-opioid receptor homodimers involving the fourth transmembrane helix.
abstract: Several G protein-coupled receptors (GPCRs), including opioid receptors deltaOR, muOR, and kappaOR, have been reported to form stable dimers or oligomers in lipid bilayers and cell membranes. This notion has been recently challenged by imaging data supporting a transient nature of GPCR association. Here we use umbrella sampling reconstructed free energies of deltaOR homodimers involving the fourth transmembrane helix to predict their association constant. The results of these simulations, combined with estimates of diffusion-limited association rates, suggest a short lifetime for deltaOR homodimers in the membrane, in agreement with recent trends.
authors.affiliation: Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Davide
authors.initials: D
authors.lastname: Provasi
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Johnston
authors.forename: Marta
authors.initials: M
authors.lastname: Filizola
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004058:Diffusion; D006207:Half-Life; D006801:Humans; D008565:Membrane Proteins; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D043562:Receptors, G-Protein-Coupled; D017465:Receptors, Opioid, delta / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D008565:Membrane Proteins; D043562:Receptors, G-Protein-Coupled; D017465:Receptors, Opioid, delta