Format

Send to

Choose Destination
See comment in PubMed Commons below
Phys Chem Chem Phys. 2014 Apr 14;16(14):6398-406. doi: 10.1039/c3cp53962h. Epub 2014 Jan 21.

Free energy landscape of G-protein coupled receptors, explored by accelerated molecular dynamics.

Author information

1
Howard Hughes Medical Institute, University of California at San Diego, La Jolla, CA 92093, USA. yimiao@ucsd.edu.

Abstract

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 Arg(3.50)-Glu(6.30) ionic lock, the Trp(6.48) toggle switch and the hydrogen interactions between Tyr(5.58)-Tyr(7.53).

PMID:
24445284
PMCID:
PMC3960983
DOI:
10.1039/c3cp53962h
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Royal Society of Chemistry Icon for PubMed Central
    Loading ...
    Support Center