Discussion on the mechanism of Shenghui Granule acting on GABAaR and AChE based on molecular docking and molecular dynamics simulation
Objective:Using molecular docking and molecular dynamics simulation to study the mechanism of action of active ingredients of Shenghui Granule on γ-aminobutyric acid type A receptor(GABAaR)and acetylcholinesterase(AChE).Methods:Collect the active ingredients of Shenghui Granule.All components were docked with GABAaR and AChE respectively by using LibDock,followed by analysis of interacting residues.Perform 30 ns molecular dynamics simulation on the best binding conformation to analyze binding stability and binding energy.Results:A total of 26 active ingredients of Shenghui Granules were collected.Molecular docking showed that there were 18 components superior to diazepam(DZP),and the best component was Acteoside.There were 4 components superior to donepezil(DNPQ),and the best component was Polygalaxanthone Ⅲ.Molecular dynamics simulations showed that GABAaR could be stably combined with Acteoside,and the binding energy was(-29.60±3.53)kcal/mol.Polygalaxanthone Ⅲ could be stably combined with AChE stably for 7 ns,then breaks away from the binding site,and re-entered in the binding site at 27-27.5 ns,and its binding energy was(-14.12±3.03)kcal/mol at 4-6 ns and(-8.16±2.95)kcal/mol at 27-27.5 ns,respectively.Conclusion:The potential ingredients of Shenghui Granules in treating insomnia and AD are Acteoside and Polygalaxanthone Ⅲ,respectively.
Shenghui GranuleMolecular dockingMolecular dynamics simulationγ-aminobutyric acid type A receptor(GABAaR)Acetylcholinesterase(AChE)
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