UC San Diego
Free energy landscape of G-protein coupled receptors, explored by accelerated molecular dynamics
- Author(s): Miao, Y
- Nichols, SE
- McCammon, JA
- et al.
Published Web Locationhttp://dx.doi.org/10.1039/C3CP53962H
G-protein coupled receptors (GPCRs) mediate cellular responses to various hormones and neurotransmitters and are important targets for treating a wide spectrum of diseases. They are known to adopt multiple conformational states (e.g., inactive, intermediate and active) during their modulation of various cell signaling pathways. Here, the free energy landscape of GPCRs is explored using accelerated molecular dynamics (aMD) simulations as demonstrated on the M2 muscarinic receptor, a key GPCR that regulates human heart rate and contractile forces of cardiomyocytes. Free energy profiles of important structural motifs that undergo conformational transitions upon GPCR activation and allosteric signaling are analyzed in detail, including the Arg3.50-Glu6.30ionic lock, the Trp6.48toggle switch and the hydrogen interactions between Tyr5.58-Tyr7.53. © 2014 the Partner Organisations.
Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.