Journal
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
Volume 14, Issue 8, Pages 4467-4473Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jctc.8b00216
Keywords
-
Funding
- German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) [CO 1715/1-1]
- French National Research Agency (Agence Nationale de la Recherche, ANR)
- U.S. National Science Foundation (NSF) as part of the Collaborative Research in Computational Neuroscience
- French government, through the UCAJEDI Investments in the Future project [ANR-15-IDEX-01]
Ask authors/readers for more resources
A replica-exchange protocol remarkably enhances the sampling of the activation dynamics of the neurotensin receptor type 1, a G protein-coupled receptor (GPCR) and important drug target. Our work highlights the dynamic communication between conformational changes of the agonist and the G protein-binding site, via contraction-oscillation of the orthosteric pocket. It also gives insights into the mechanism by which certain mutations diminish or stimulate activation. The replica-exchange protocol effectively enhances barrier crossing where standard brute-force molecular dynamics simulations fail. It is readily applicable to other GPCRs and represents a promising approach for virtual ligand screening, using the typical features of receptor activation as a benchmark.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available