The Near Attack Conformation (NAC) approach states that the efficiency of an enzyme-catalyzed reaction depends on the prior attainment of optimal conditions for substrate atom organization and positioning for bond formation. These conditions are prerequisites for the transition state (TS) in which the involved atoms are within the van der Waals range of contact and positioned at an angle similar to that achieved after bond formation. The successful application of this approach to investigate the reactivation mechanism of acetylcholinesterase inhibited by nerve agents has contributed to a better understanding of this mechanism and demonstrated consistent corroboration with experimental data. In this article, we summarize the accomplishments achieved thus far and outline future perspectives.

Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanskeho 62 50003 Hradec Kralove Czech Republic

Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanskeho 62 50003 Hradec Kralove Czech Republic; Institute of Chemical Biological Radiological and Nuclear Defense Rio de Janeiro RJ Brazil

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

Laboratory of Molecular Modeling Applied to Chemical and Biological Defense Military Institute of Engineering Rio de Janeiro Brazil; Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanskeho 62 50003 Hradec Kralove Czech Republic

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Synthesis and in vitro assessment of the reactivation profile of clinically available oximes on the acetylcholinesterase model inhibited by A-230 nerve agent surrogate