MMSL 2013, 82(3):102-114 | DOI: 10.31482/mmsl.2013.015

MODELING THE BINDING OF CWAs TO AChE AND BuChEOriginal article

Brian J. Bennion1, Edmond Y. Lau1, Jean-Luc Fattebert2, Patrick Huang3, Eric Schwegler3, William Corning4, Felice C. Lightstone1*
1 Biosciences and Biotechnology Division, Mailstop L-372, Lawrence Livermore National Laboratory, 7000 East Ave, Livermore CA, 94550.
2 Computation Directorate Mailstop L-561, Lawrence Livermore National Laboratory, 7000 East Ave Livermore CA 94550.
3 Condensed Matter and Materials Division, Mailstop L-198, Lawrence Livermore National Laboratory, 7000 East Ave Livermore CA 94550.
4 Deer Valley High School, 4700 Lone Tree Way, Antioch, CA 94531

Traditional chemical weapon agents (CWAs) are known to bind acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Their lethality is known to be different for different mammalian species. We have modeled the binding affinity of CWAs to AChE and BuChE in human, rabbit, rat and mouse using molecular docking and free energy calculations. Through molecular docking we are able to correctly bind the CWAs at the active site. Using molecular mechanics generalized Born surface area (MMGBSA) calculations, we determined the binding free energy in the active site. Through these calculations, we observe that correct orientation at the active site is critical to binding.

Keywords: AChE; BuChE; computational docking; molecular dynamics simulations; binding free energy calculations

Received: February 10, 2013; Revised: March 25, 2013; Published: September 6, 2013  Show citation

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Bennion, B.J., Lau, E.Y., Fattebert, J., Huang, P., Schwegler, E., Corning, W., & Lightstone, F.C. (2013). MODELING THE BINDING OF CWAs TO AChE AND BuChE. MMSL, 82(3), 102-114. doi: 10.31482/mmsl.2013.015
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