Parametrization of Ligands Associated with the RNA Dependent RNA Polymerase Found in Hepatitis C Virus

Abstract

Hepatitis C virus (HCV) is a wide spread health concern and affects approximately 35,000 new cases in the U.S. each year. Though there are treatments available, they cause many unpleasant side effects and are not completely effective. HCV contains a positive sense single-stranded RNA genome and replicates with the aid of RNA Dependent RNA polymerase (RdRp). Certain naturally occurring ligands have been found to exhibit allosteric properties towards RdRp. These inhibitors are termed “allosteric” because they bind to the enzyme at locations other than the activation site.Our goal is to discover the properties of such ligands that bond to the enzyme in this manner. We will computationally model these chemicals and compare them to others that may demonstrate the same traits in order to take a multi-faceted approach to allosterically inhibit RdRp.By utilizing programs such as CHARMM (Chemistry at HARvard Molecular Mechanics) and Gaussian, as well as molecular visualization programs, we will model and view the ligands to further understand the properties that make them unique.The information obtained from our computational modeling of the ligands will be compiled and processed with the information obtained from the protein they bind to and combined together to determine the nature of their interaction.