Tabun is one of the most dangerous nerve agents because it has deleterious effects like inhibition of the essential enzymes acetylcholinesterase (AChE) and butyrylcholinesterase. Some oximes such HI6 as 2-PAM are nucleophiles that are capable to reactivate inhibited human AChE under some conditions. Zwitterionic and cationic species have the best chance of productive action on inhibited AChE. However uncharged oximes can give important interaction information. In order to investigate the interaction and behavior of cationic and uncharged oximes, we performed molecular docking simulations and molecular dynamics and calculated binding energies of complexes of these compounds with human AChE. The uncharged oximes of larger structure were more susceptible to the influence of the substituents on the phosphorus atom and presented low binding energies. In contrast, HI 6 and 2-PAM showed high binding energy values with great contribution of the amino acid Asp74, demonstrating the importance of the quaternary nitrogen to the affinity and interaction of the oximes/AChE tabun-inhibited complexes.

b Faculty of Technology University of the State of Rio de Janeiro Resende Brazil

c Center for Basic and Applied Research Faculty of Informatics and Management University of Hradec Králové Hradec Králové Czech Republic

e Chemistry Institute Federal University of Rio de Janeiro Rio de Janeiro Brazil

Laboratory of Molecular Modeling Applied to Chemical and Biological Defense Military Institute of Engineering Rio de Janeiro Brazil

University Hospital Hradec Králové Hradec Králové Czech Republic

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Molecular Modeling Study of Uncharged Oximes Compared to HI-6 and 2-PAM Inside Human AChE Sarin and VX Conjugates