Parameterization of the GPR119 Receptor Agonist AR231453
| Autor: | Evangelia Kotsikorou, John Hamilton |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class Pharmacology Molecular Dynamics Simulation Ligands 01 natural sciences Receptors G-Protein-Coupled 03 medical and health sciences Molecular dynamics 0103 physical sciences medicine Gpr119 agonist Receptor Ligand molecule Oxadiazoles 010304 chemical physics Molecular Structure Chemistry General Chemistry Computational Mathematics 030104 developmental biology GPR119 Pyrimidines Mechanism of action Biophysics medicine.symptom Receptor activation |
| Zdroj: | Journal of computational chemistry. 39(1) |
| ISSN: | 1096-987X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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