Parameterization of AR231453: A Potent Agonist of the GPR119 Receptor, a Target for Diabetes Treatment

Author

John E. Hamilton, The University of Texas Rio Grande Valley

Date of Award

5-2017

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Dr. Evangelia Kotsikorou

Second Advisor

Dr. Frank Dean

Third Advisor

Dr. Jason Parsons

Abstract

The first reported potent agonist for the GPR119 receptor, a potential target for the treatment of diabetes, is 2-fluoro-4-methanesulfonyl-phenyl-{6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-amine (AR231453). The dynamic interactions of AR231453 with GPR119 using molecular dynamics simulation are of great interest. However, parameters for AR231453 that describe the behavior of the molecule in the CHARMM force field have not been determined. The following study produces parameters by creating model fragments and compares the produced parameters to quantum calculations. The produced parameters are then further refined within the Visual Molecular Dynamics (VMD) program’s plugin program, the Force Field Toolkit as well as Gaussian 09 and CHARMM. Molecular dynamics simulations are done to study the orientation of AR231453 in a lipid bilayer.

Comments

Copyright 2017 John E. Hamilton. All Rights Reserved.

https://www.proquest.com/dissertations-theses/parameterization-ar231453-potent-agonist-gpr119/docview/1964913926/se-2?accountid=7119

Recommended Citation

Hamilton, John E., "Parameterization of AR231453: A Potent Agonist of the GPR119 Receptor, a Target for Diabetes Treatment" (2017). Theses and Dissertations. 120.
https://scholarworks.utrgv.edu/etd/120