Inhibitory Activity of Natural Flavonoids against Protein Aggregation in Alzheimer’s disease: A Computational Simulation Study

In this study, the prevention mechanism of chrysin, datiscetin, naringenin, and wogonin against Aβ peptide and tau protein aggregation was investigated using computational simulation methods. According to the molecular docking data, minor differences in the chemical structures of candidate compounds do not result in significant differences in docking binding energy. Instead, the ligand binding site and residue contact degree appear to have played a more significant role. Naringenin showed the highest affinity for tau protein due to its different binding site. Because of more residue contacts, chrysin and datiscetin also had a higher amyloid binding affinity. The secondary structure analysis of amyloid β revealed a significant loss of α-helix content in all systems studied with the formation of turns and random coils, which is most in the presence of wogonin. In all tau-ligand systems, the percentage of the coil decreased. In contrast, the turn percentage increased, indicating that the selected compounds can prevent the aggregation of AD-related receptors.