Molecular Modeling to Develop Better Reactivators (sponsored by Department of Defense/DTRA)
Nerve agents are a continuing threat, both in wartime and as potential terrorist weapons. Currently, a number of oximes have been deployed or are under consideration as treatment for nerve agent exposure. But one of the primary problems with developing new treatments is a lack of knowledge of how these compounds interact with their target protein on the atomic level and of the atomic-scale forces and interactions that determine the efficacy of an oxime. This project uses molecular modeling to provide a better understanding of the reaction by which oximes reactivate cholinesterases that have been inhibited by nerve agents. The goal is to aid in developing new therapeutics via rational drug design using the information generated by this project.