Author : Brittny C. Davis
Publisher :
ISBN 13 :
Total Pages : 322 pages
Book Rating : 4.:/5 (958 download)
Book Synopsis Determining the Molecular Origins of Allostery for the Polymerase from the Hepatitis C Virus by : Brittny C. Davis
Download or read book Determining the Molecular Origins of Allostery for the Polymerase from the Hepatitis C Virus written by Brittny C. Davis and published by . This book was released on 2015 with total page 322 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hepatitis C virus (HCV) infects 170 million people worldwide, and approximately 3-4 million people within the United States. To date, there is no cure for this disease, and 25% of individuals living with HCV contract chronic liver ailments such as cirrhosis or liver cancer. The HCV RNA polymerase (gene product NS5B) has become a drug target because of its importance in viral replication. Several small molecules have been identified that inhibit NS5B and bind outside of the active site; these are referred to as allosteric inhibitors. There are four different allosteric binding sites that have been identified, and several crystal structures of NS5B enzyme bound to various inhibitors exist. However, a mechanism of inhibition is unclear from the structural data alone and has yet to be conclusively determined. We hypothesize that one can understand the effect of allosteric inhibitors on the functional properties of NS5B by using molecular dynamics simulations to study the enzyme in a free state and bound to various inhibitors. Molecular dynamics is an optimal tool to study this problem because it can provide information about both structure and dynamics at the molecular level. By understanding the structural, dynamic, and thermodynamic changes that accompany ligand binding, we hope to determine the molecular origins of allosteric inhibition in NS5B. In the process we will gain essential information on how NS5B and other viral polymerases replicate RNA. 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 NS5B, and ultimately better treatments for HCV.