A Molecular Mechanics Study of Natural Product Polyphenols Interacting with beta-Amyloid

Abstract

The most common form of neurodegenerative dementia is Alzheimer’s disease. One of the hallmarks of the disease is the presence of plaques, which is an aggregation of a peptide called amyloid-β. This aggregation occurs because of misfolding of the protein. Recent studies have shown that polyphenols within different types of foods may have potential to have an anti-aggregate effect on amyloid-β. This study focused on using molecular modeling to dock various polyphenols to two regions on the amyloid β-peptide: H13HQK and L17VFF. These areas are often targeted by anti-aggregate drugs for Alzheimer’s. The polyphenols that were studied were (+)-catechin, (-)-epicatechin, cyanidin, and quebecol. An analysis of binding energies and interactions obtained using the CHARMM22 force field showed that these molecules have some affinity to HHQK but more so toward LVFF. Cyanidin, however, showed very little affinity to HHQK.