Date of Award

2012

Document Type

Thesis

Department

Chemistry

First Reader

Dr. Martin D. "Marty" Perry

Second Reader

Dr. Kevin Cornelius

Third Reader

Dr. Sara Hubbard

Abstract

Studies have shown that CYP2E1, a cytochrome P450 enzyme containing two primary binding sites, plays a substantial role in the oxidative metabolism of many foreign substances, including the detoxification reaction of 4-nitroanisole to 4-nitrophenol. Through the advancements of the 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 Surflext and molecular dynamics, have created the ability to ascertain the likely binding configurations of 4-nitranisole 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 plays in human oxidative metabolism of xenobiotic substances. The goal in this research was to observe the configuration of nitroanisole and its derivatives in relation to the heme of the enzyme and possibly determine a cause for the unconventional reaction kinetics of CYP2E1.

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