Bennion_2013_Mil.Med.Sci.Lett_82_102

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.