Reactivation steps by 2-PAM of tabun-inhibited human acetylcholinesterase: reducing the computational cost in hybrid QM/MM methods

J Biomol Struct Dyn. 2014;32(2):301-7. doi: 10.1080/07391102.2013.765361. Epub 2013 Mar 25.

Abstract

The present work describes a simple integrated Quantum Mechanics/Molecular Mechanics method developed to study the reactivation steps by pralidoxime (2-PAM) of acetylcholinesterase (AChE) inhibited by the neurotoxic agent Tabun. The method was tested on an AChE model and showed to be able to corroborate most of the results obtained before, through a more complex and time-consuming methodology, proving to be suitable to this kind of mechanistic study at a lower computational cost.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / metabolism
  • Cholinesterase Inhibitors / pharmacology*
  • Cholinesterase Reactivators / chemistry
  • Cholinesterase Reactivators / pharmacology*
  • Humans
  • Molecular Docking Simulation
  • Organophosphates / antagonists & inhibitors*
  • Organophosphates / chemistry
  • Organophosphates / pharmacology
  • Pralidoxime Compounds / chemistry
  • Pralidoxime Compounds / pharmacology*

Substances

  • Cholinesterase Inhibitors
  • Cholinesterase Reactivators
  • Organophosphates
  • Pralidoxime Compounds
  • Acetylcholinesterase
  • pralidoxime
  • tabun