Abstract

Severe morbidity and mortality consequences result from irreversible inhibition of human acetylcholinesterase by organophosphates (OPs). Oxime-based reactivators are currently the only available treatments but lack efficacy in the central nervous system (CNS) where the most damage occurs. Computational docking and molecular dynamics (MD) simulations reveal complex structural barriers that may reduce oxime efficacy. These results may guide future drug designs of more effective countermeasures.

Disciplines

Biochemistry | Biophysics | Computational Neuroscience | Enzymes and Coenzymes | Medical Biophysics | Molecular and Cellular Neuroscience | Organic Chemicals | Other Biochemistry, Biophysics, and Structural Biology | Pharmaceutics and Drug Design

Mentor

Brian Bennion

Lab site

Lawrence Livermore National Laboratory (LLNL)

Funding Acknowledgement

This material is based upon work supported by the S.D. Bechtel, Jr. Foundation and by the National Science Foundation under Grant No. 0952013 and Grant No. 0833353. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the S.D. Bechtel, Jr. Foundation or the National Science Foundation. This project has also been made possible with support of the National Marine Sanctuary Foundation. The STAR program is administered by the Cal Poly Center for Excellence in Science and Mathematics Education (CESaME) on behalf of the California State University (CSU).

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URL: https://digitalcommons.calpoly.edu/star/196

 

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