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Updated: Jul 20, 2026

Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
Parameterization of the GPR119 Receptor Agonist AR231453
John Hamilton1, Evangelia Kotsikorou1
1Department of Chemistry, The University of Texas Rio Grande Valley, 1201 W. University Dr. Edinburg, Texas, 78539-2999.
Abstract:
The GPR119 receptor is a class A G protein-coupled receptor expressed mainly in pancreatic beta cells. Since GPR119 receptor activation ameliorates Type 2 Diabetes through an increase in glucose-dependent insulin release, the development of new GPR119 receptor agonists would be worthwhile. A better understanding of the way agonists interact with the receptor would help to design better ligands for the receptor. It also would help to better understand the agonist mechanism of action. An understanding of how agonists interact with the receptor can be acquired using molecular dynamics simulations, which cannot be performed without having force field parameters for the ligand molecule. This study presents the development of CHARMM force field parameters for AR231453, the prototypical first potent and orally available GPR119 agonist, using the Force Field Tool Kit. The parameters are validated through Normal Mode Analysis calculations and molecular dynamics simulations in combination with infrared spectroscopy. © 2017 Wiley Periodicals, Inc.
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