Recent Insights from Molecular Dynamics Simulations for G Protein-Coupled Receptor Drug Discovery
Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(17), 4237; https://doi.org/10.3390/ijms20174237
Received: 13 July 2019
/
Revised: 26 August 2019
/
Accepted: 27 August 2019
/
Published: 29 August 2019
(This article belongs to the Special Issue Computer Simulation on Membrane Receptors)
G protein-coupled receptors (GPCRs) are critical drug targets. GPCRs convey signals from the extracellular to the intracellular environment through G proteins. Some ligands that bind to GPCRs activate different downstream signaling pathways. G protein activation, or β-arrestin biased signaling, involves ligands binding to receptors and stabilizing conformations that trigger a specific pathway. β-arrestin biased signaling has become a hot target for structure-based drug discovery. However, challenges include that there are few crystal structures available in the Protein Data Bank and that GPCRs are highly dynamic. Hence, molecular dynamics (MD) simulations are especially valuable for obtaining detailed mechanistic information, including identification of allosteric sites and understanding modulators’ interactions with receptors and ligands. Here, we highlight recent MD simulation studies and enhanced sampling methods used to study biased G protein-coupled receptor signaling and their conformational dynamics as well as applications to drug discovery.
View Full-Text
Keywords:
GPCRs; membrane protein; molecular dynamics; protein structure; drug design; biased-signaling pathway; allosteric sites
▼
Show Figures
Graphical abstract
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
MDPI and ACS Style
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. https://doi.org/10.3390/ijms20174237
AMA Style
Zou Y, Ewalt J, Ng H-L. Recent Insights from Molecular Dynamics Simulations for G Protein-Coupled Receptor Drug Discovery. International Journal of Molecular Sciences. 2019; 20(17):4237. https://doi.org/10.3390/ijms20174237
Chicago/Turabian StyleZou, Ye, John Ewalt, and Ho-Leung Ng. 2019. "Recent Insights from Molecular Dynamics Simulations for G Protein-Coupled Receptor Drug Discovery" International Journal of Molecular Sciences 20, no. 17: 4237. https://doi.org/10.3390/ijms20174237
Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
