Both molecular docking and molecular dynamics was used to visualise the active or blocked site of AChE, and to determine affinity values in silico modelling. Selection of 60 ligands (including commercially available reactivators, e.g. trimedoxime, asoxime) from peer-reviewed articles (2) were docked into into proximity of AChE-A230 complex bond using software AutoDock Vina (v. 1.1.2). The most promising 32 ligands docked in AChE were evaluated by molecular dynamics (GROMACS 2020.4 software).
Evaluation of specified simulations using Visual Molecular Dynamics (VMD) software has shown that the closest distance between the oxime group of the Z03-labeled ligand and the phosphorus of A230 was 3.14Å proposing theoretical successful reactivation regarding the near–attack conformation (NAC) criterion. The results of this study provide a rational basis for the synthesis of proposed reactivators and their consecutive in vitro evaluation.

Keywords: novichok agents; acetylcholinesterase; reactivators; in silico