Chemistry and Biochemistry
Area of Doctoral Study: Chemistry
Undergraduate Institute: Universidad Autonoma de Madrid
Research Advisor: Ian Thorpe, Ph.D.
Description of Research
Hepatitis C virus (HCV) is a global health concern. There are approximately 3-4 million new cases of HCV infection each year, with an estimated 2-3% of the world population (130-170 million people, 5 million in the US alone) chronic carriers of HCV. HCV contains a positive sense single-stranded RNA genome and replicates with the aid of an RNA-dependent RNA polymerase (viral gene product NS5B). This enzyme has been the object of numerous studies in the last decade as a target for HCV antiviral drugs. It is thought to exhibit open and closed conformations associated with the initiation and elongation stages, respectively, of RNA replication. In our work we employ extensive Molecular Dynamics (MD) simulations to understand, at the molecular level, the structural and dynamic features associated with the conformational states sampled by the enzyme. Our ultimate goal is to understand the mechanisms by which transitions between these states occur and to determine how conformational changes impact the properties of the enzyme. This knowledge is essential to elucidate the role of conformational sampling in governing RNA replication by NS5B and may also be valuable in understanding the basis of enzyme inhibition. Once we understand how the enzyme works and what the mechanism of transition between the conformations is we will be able to point out key residues that will be good targets for new drugs to inhibit NS5B.