Lessons from free energy simulations of delta-opioid receptor homodimers involving the fourth transmembrane helix

Biochemistry. 2010 Aug 10;49(31):6771-6. doi: 10.1021/bi100686t.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Computer Simulation*
  • Diffusion
  • Half-Life
  • Humans
  • Membrane Proteins
  • Protein Multimerization*
  • Protein Structure, Secondary
  • Receptors, G-Protein-Coupled
  • Receptors, Opioid, delta / chemistry*
  • Receptors, Opioid, delta / metabolism
  • Thermodynamics*

Substances

  • Membrane Proteins
  • Receptors, G-Protein-Coupled
  • Receptors, Opioid, delta