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Updated: Feb 8, 2026

Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
Activation Dynamics of the Neurotensin G Protein-Coupled Receptor 1
Xiaojing Cong1, Sébastien Fiorucci1, Jérôme Golebiowski1,2
1Université Côte d'Azur, CNRS , Institut de Chimie de Nice UMR7272 , 06108 Nice , France.
Abstract:
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.
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