Next Article in Journal
Cafestol and Kahweol: A Review on Their Bioactivities and Pharmacological Properties
Next Article in Special Issue
A Molecular Dynamics Study of Vasoactive Intestinal Peptide Receptor 1 and the Basis of Its Therapeutic Antagonism
Previous Article in Journal
Cyclin–CDK Complexes are Key Controllers of Capacitation-Dependent Actin Dynamics in Mammalian Spermatozoa
Previous Article in Special Issue
Deciphering the Molecular Recognition Mechanism of Multidrug Resistance Staphylococcus aureus NorA Efflux Pump Using a Supervised Molecular Dynamics Approach
Open AccessReview

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 GPCRs; membrane protein; molecular dynamics; protein structure; drug design; biased-signaling pathway; allosteric sites
Show Figures

Graphical abstract

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.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop