QSAR, docking, and Molecular dynamic studies on the polyphenolic as inhibitors of β-amyloid aggregation

Abstract

Alzheimer’s disease is causally linked to the aggregation of amyloid-β peptide and is one of the main causes of death in developed countries. Consumption of foods rich in polyphenolics is strongly correlated to reduced occurrence rate of Alzheimer’s disease. This paper compares the inhibition effect of amyloid-β aggregation in the presence of 25 polyphenolic compounds by quantitative structure–activity relationship (QSAR), molecular docking, and molecular dynamics simulation. The structure information such as solvent accessible surface area and radial distribution function was obtained at 300 K. The results showed that three compounds, luteolin, transilitin, and maritimetin, were identified as potent inhibitors of Aβ aggregation. Interaction energies between polyphenolic derivatives and β-amyloid were obtained using docking calculation. Computational docking studies offer a rational discussion for the observed inhibitory activity. Multiple linear regression method and principal component analysis were used to set up QSAR models for predicting anti-Alzheimer activity of 25 polyphenolics derivatives. These computational studies may facilitate in understanding the action mechanism and development of improved inhibitors of Aβ aggregation or modification of this series of the anti-Alzheimer agents.