Assessing Inhibitory potential of natural compounds against BACE1 in Alzheimer's disease: A molecular docking and molecular dynamics simulation approach

Abstract

10% of people over 65 are affected by Alzheimer's disease (AD), worldwide health issue. It is believed that genetic, cellular, and multifactor pathophysiological pathways are responsible for the development of AD and other neurodegenerative diseases. BACE1, or Beta-site amyloid precursor protein cleaving enzyme 1, is an enzyme that plays a key role in the formation of amyloid-beta (Aβ) peptides in the brain. Aβ peptides are a hallmark characteristic of AD. The current work used highly developed computational biology technologies to find ligands that could bind to protein targets effectively in the context of AD. The aim of the current investigation was to determine the efficiency of a small chemical library against the BACE1. Our study enlightens the inhibitory role of phytocompounds against BACE1 through in silico approaches including molecular docking using Autodock Vina and molecular dynamics simulation. Thus in this study, we have elucidated the potential of best reported phytocompounds as potent inhibitors of Alzheimer’s disease. Molecular docking was performed between 163 potent compounds to identify best potential inhibitor which could inhibit the BACE1. Out of 163 compounds Subtrifloralactone A and B, two natural chemicals, have demonstrated sufficient interactions with the active site residues depending on the AutoDock Vina binding affinity. These compounds' respective binding affinity were discovered to be -11.0 kcal/mol and -11.0 kcal/mol. Virtual screening of 1031 chemical compounds revealed that only two chemical compounds are having best interactions with BACE1 and might be the potential inhibitor(s) of the BACE1. Further, molecular dynamics simulation of these two chemical compounds revealed that subtrifloralactone A and subtrifloralactone B which belongs to the steroid group of compounds shows the stable activity with the BACE1.Additional experimental validation could confirm the inhibitory activity of the potential candidates.