Ứng dụng mô hình mô phỏng docking để so sánh tương tác giữa các thuốc kháng cholinergic với enzyme acetylcholinesterase

Abstract

In this study, molecular docking using AutoDock was utilized to analyze interactions between several promising drugs (tacrine, rivastigmine, galantamine, and donepezil) and acetylcholinesterase (AChE). The X-ray structure of AChE (PDB: 4EY6) from Protein Data Bank was used for molecular modeling simulation software (AutoDock Vina, AutoGrid4, and AutoDock4). Binding free energies of docking calculations were generated by the automatic docking method of Lamarckian genetic algorithm (LGA). Inhibitory effects of ligands were analyzed by Discovery Studio Visualizer software, which showed important interactions such as hydrogen bond, hydrophobic interaction, pi-stacking interaction between aromatic amino acids and drugs. Based on results obtained from LGA and Discovery Studio Visualizer software, the important interactions between these anticholinergic inhibitors and the active site residues were determined. This study can be further used for the virtual screening approach of house database compounds against Alzheimer’s disease.