TCBG Seminar

Insights into the Activation Pathway of the Adenovirus Protease Enzyme using Nudged Elastic Band Simulations

Professor Ross C. Walker
San Diego Supercomputer Center
University of California, San Diego
La Jolla, CA

Monday, April 21, 2008
3:00 pm (CT)
3269 Beckman Institute


The adenovirus proteinase (AVP) is essential for adeno virus replications and hence is a target for antiviral drugs aimed at treating infections such as bird-flu and SARS. The enzyme is activated upon the binding of a small peptide via a 53 amino acid signal transduction pathway. Recently obtained crystal structures of both the inactive and active forms of AVP provide the two end points of this pathway. This talk will highlight attempts, in combination with experimentalists at Brookhaven National Laboratory, to characterize this pathway. This includes a combination of standard molecular dynamics simulations, replica exchange simulations and a complete characterization of the structural motions involved in the activation pathway using a simulating annealing based Nudged Elastic Band (NEB) algorithm that is implemented within the AMBER software. Simulations to date have revealed some interesting features of this pathway and it is hoped that this insight, coupled with experimental feedback, will provide valuable data that can aid in identifying novel drug targets other than the active site and in finding drugs that prevent the utilization of the pathway.

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