Thursday, October 2, 2008
Salon B and C (The Peabody Little Rock)

Computational Docking Investigations of Oxidative Metabolism of 4-Nitroanisole with CYP2E1

Abby Brumley, Ouachita Baptist University, Arkadelphia, AR, Marty Perry, Ouachita Baptist University, Arkadelphia, AR, and Grover P. Miller, University of Arkansas for Medical Sciences, Little Rock, AR.

CYP2E1, a cytochrome P450 enzyme, plays a substantial role in the oxidative metabolism of many foreign substances, including the detoxification reaction of 4-nitroanisole to 4-nitrophenol. These reactions may depend on the presence of two binding site that influence the clearance of these molecules. Through the advancements of computational docking software Tripos Sybyl7.2, it has been possible to investigate the mechanism of oxidation of 4-nitroanisole. Docking modules of Sybyl7.2 software including Suflex and molecular dynamics have created the ability to assertain the likely binding configurations of 4-nitroanisole and its constitutional isomers in either the distal or proximal binding sites of CYP2E1. Knowing the relative binding relationships of 4-nitroanisole to the heme of the CYP2E1 enzyme, further experimentation may be conducted to determine the actual role that CYP2E1 plays in human oxidative metabolism of xenobiotic substances.