Graded activation and free energy landscapes of a muscarinic G-protein–coupled receptor
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- Yinglong Miao
- Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093;
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- J. Andrew McCammon
- Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093;
書誌事項
- 公開日
- 2016-10-10
- 権利情報
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- http://www.pnas.org/site/misc/userlicense.xhtml
- DOI
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- 10.1073/pnas.1614538113
- 公開者
- National Academy of Sciences
この論文をさがす
説明
<jats:title>Significance</jats:title> <jats:p> G-protein–coupled receptors (GPCRs) represent primary targets of about one-third of currently marketed drugs. The structure, dynamics, and function of GPCRs result from complex free energy landscapes. In this work, we have applied Gaussian accelerated molecular dynamics (GaMD) to study the ligand-dependent behavior of the M <jats:sub>2</jats:sub> muscarinic GPCR. Extensive GaMD simulations have revealed distinct structural flexibility and free energy profiles that depict graded activation of the M <jats:sub>2</jats:sub> receptor. We have captured both dissociation and binding of an orthosteric ligand in a single all-atom GPCR simulation. GaMD is well poised to study large biomolecules and ligand recognition for drug discovery. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 113 (43), 12162-12167, 2016-10-10
National Academy of Sciences
