Zou, Y.; Ewalt, J.; Ng, H.-L. Recent Insights from Molecular Dynamics Simulations for G Protein-Coupled Receptor Drug Discovery. Int. J. Mol. Sci.2019, 20, 4237.
Zou, Y.; Ewalt, J.; Ng, H.-L. Recent Insights from Molecular Dynamics Simulations for G Protein-Coupled Receptor Drug Discovery. Int. J. Mol. Sci. 2019, 20, 4237.
Zou, Y.; Ewalt, J.; Ng, H.-L. Recent Insights from Molecular Dynamics Simulations for G Protein-Coupled Receptor Drug Discovery. Int. J. Mol. Sci.2019, 20, 4237.
Zou, Y.; Ewalt, J.; Ng, H.-L. Recent Insights from Molecular Dynamics Simulations for G Protein-Coupled Receptor Drug Discovery. Int. J. Mol. Sci. 2019, 20, 4237.
Abstract
G protein-coupled receptors (GPCRs) are critical drug targets. GPCRs convey signals from the extracellular to the intracellular environment through G proteins. There is evidence that some ligands that bind to the GPCRs activate different downstream signaling pathways. G protein activation or -arrestin biased signaling involves ligands binding to receptors and stabilizing conformations that trigger a specific pathway. Molecular dynamics (MD) simulations are especially valuable for obtaining detailed mechanistic information, including identification of allosteric sites and understanding modulators' interactions between receptors and ligands. Here, we highlight recent simulation studies and methods used to study biased G protein-coupled receptor signaling and their conformational dynamics. We also highlight applications of MD simulations to drug discovery.
Keywords
GPCRs; membrane protein; molecular dynamics; protein structure; drug design; biased-signaling pathway; allosteric sites
Subject
Biology and Life Sciences, Biophysics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
