Chemistry and Biochemistry 2015
Area of Doctoral Study: Chemistry
Undergraduate Institute: Jackson State University
Graduate Institute: Johns Hopkins University, MPH (Cancer Prevention Program)
Research Advisor: Ian Thorpe, Ph.D.
Current Position: Postdoctoral Fellow, National Cancer Institute (NCI) Cancer Prevention Program
Description of Research
The Hepatitis C Virus (HCV) affects 170 million people throughout the world. About 25% of individuals living with HCV will eventually contract chronic liver ailments and possibly suffer from severe complications such as cirrhosis or liver cancer. These ailments can eventually lead to liver failure. Currently, there is no cure for this disease and the current treatments, interferon and ribavarin, are only effective for very few people. The RNA polymerase from HCV (RdRp) is an enzyme that is presently a target protein for drug discovery because of its importance for viral replication. Several non-nucleoside inhibitors of the enzyme have been identified. The mechanism of action of these inhibitors is unknown. We hypothesize that one can understand the effects of these inhibitors on RdRp by using molecular dynamics (MD) simulations to study the dynamics of the enzyme, both in a free state and bound to various inhibitors. Results from MD simulations can help relate the structure and dynamics of the enzyme to its function. MD is an optimal tool to study this problem because it can provide information about both structure and dynamics at a level of fine detail. By observing the structural coupling, which occurs as a result of enzyme dynamics, we hope to delineate the function of ligand binding in RdRp inhibition. Besides illuminating fundamental questions regarding the link between enzyme function and dynamics, this information may aid in the development of novel and more effective inhibitors for RdRp.