Combining Virtual Screening, Molecular Docking and Simulation studies towards the discovery of β-secretase (BACE) inhibitors

Abstract

β-secretase (BACE) is an enzyme that is encoded by BACE1 gene. It is also known as beta-site amyloid precursor protein cleaving enzyme. The BACE enzyme is mainly associated with the filamentous aggregation of amyloid, leads in the formation of plagues in Alzheimer's disease. The present study is conducted to explore phytochemicals constituents of North East India particularly Bacopa monneiri, Galanthus woronowii, Ginkgo bibola, Narcissus leonensis, Piper nigrum and Emblica officinalis known to possess anti-alzheimer properties. The compounds of these 6 plants were retrieved from publically available databases PubChem, ChEBI and ZINC database. The compounds were further forwarded for virtual screening followed by molecular docking and molecular dynamics simulation studies. Out of 500 phytochemical constituents only 4 of the compounds passed Lipinski's and drug-likeliness rule. The detailed insight of binding mechanism revealed out of virtually screened compounds Butyl-methoxy-methyl-BLAHol, 5,6-dimethyl-2-(4-piperidinylmethyl)-1-indanone hydrochloride, Epinorlycoramine and Sanguinine compounds showed that Epinorlycoramine has the highest binding energy of 8.2 Kcal/mol against the receptor BACE. The compound was later forwarded for molecular dynamic simulation for 500 ns. The simulation revealed the stability of the compounds within the receptor. Thus the compound reported in the present study may be forwarded for experimental validation and clinical studies as potent anti-alzheimer.