Molecular docking and toxicity studies of nerve agents against acetylcholinesterase (AChE)

Abstract

Acetylcholinesterase (AChE) is a cholinergic enzyme that plays an essential role in the autonomic nervous system. This enzyme is often the target of many nerve agents. When this enzyme is inhibited, its function to hydrolyze acetylcholine is stopped, accumulating the acetylcholine in the tissue and causing prolonged stimulation. Some of the significant nerve agents include sarin (GB), soman (GD), tabun (GA), and venomous agent (VX). In order to determine which compound is the most stable and has the best affinity, the nerve agent venomous agent (VX), sarin (GB), soman (GD), and tabun (GA) are docked to the acetylcholinesterase (AChE) enzyme. After that, toxicity tests will be performed on 17 targets for the compound that was chosen. Autodock Vina 1.2.0 is the software used for the docking procedure. should use the Pymol program version 2.5.4 for analysis and the Ligplot software version 2.2 for visualization of the docking findings. The 'Tox Prediction’ algorithm from Insilico was used to determine the toxicity of various substances. Based on the results of molecular docking, the free binding energy of Donepezil, sarin (GB), soman (GD), tabun (GA), and venomous agent (VX) in kcal/mol are −12,3, −4.8, −6.0, −5,1, and −6.3 respectively. Finally, four ligands bind strongly to the receptor Donepezil at RMSD 0.327 Å, and the venomous agent (VX) compound binds the most strongly compared to the other test ligands. Furthermore, in the toxicity test of Compound VX, which exhibits neurotoxic activity, no toxic activity was observed on specific organs and targets.