[LA-SiGMA] Professor Ian Thorpe - "Inhibitor Binding Eliminates Functionally Important Dynamics in the Hepatitis C Virus RNA Polymerase."

[sjlee at cct.lsu.edu]

Hello,

Professor Ian Thorpe of the University of Maryland, Department of  
Chemistry and Biochemistry will be giving a talk, titled, "Inhibitor  
Binding Eliminates Functionally Important Dynamics in the Hepatitis C  
Virus RNA Polymerase." The talk will take place at the University of  
New Orleans, March 19, 3:30 pm in the Chemistry and Science Building,  
room 103. See attachment.

Abstract:

Hepatitis C Virus (HCV) is a global health concern.  Infection can  
lead to chronic liver damage and severe complications such as liver  
failure.  There is no known cure for infection and few effective  
treatments exist.  The HCV RNA-dependent RNA polymerase (gene product  
NS5B) is a target for therapeutics due to its importance in  
replicating the viral genome.  Allosteric inhibitors of NS5B have been  
identified: these bind to the enzyme outside of the active site at  
which RNA synthesis occurs.  While their mechanism of action is  
unknown, it has been suggested that inhibitors prevent a  
conformational change in NS5B which is crucial for RNA replication.   
In this work, molecular dynamics simulations were employed to  
understand how inhibitor binding to the thumb domain of NS5B impacts  
its physical properties. These studies reveal that the presence of an  
inhibitor alters both the structure and internal motions of NS5B and  
suggests that motions eliminated by inhibitor binding may be  
functionally relevant. These studies provide insight into how  
allosteric ligands are able to inhibit NS5B and answers fundamental  
questions about how small ligands can induce allosteric effects in  
macromolecules.

If you have any questions, please let us know.

Regards,
Shelley Lee
Project Coordinator
225-578-0465
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