Inhibition Effect and Molecular Mechanisms of Quercetin on the Aβ42 Dimer: A Molecular Dynamics Simulation Study

[Image: see text] Amyloid-β (Aβ) dimer as the smallest oligomer has recently been drawing attention due to its neurotoxicity, transient nature, and heterogeneity. The inhibition of Aβ dimer’s aggregation is the key to primary intervention of Alzheimer’s disease. Previous experimental studies have reported that quercetin, the widespread polyphenolic constituent of multiple fruits and vegetables, can hamper the formation of Aβ protofibrils and disaggregate Aβ fibrils. However, the molecular mechanisms of quercetin in the suppression of the Aβ(1–42) dimer’s conformational changes still remain elusive. In this work, to investigate the inhibitory mechanisms of quercetin molecules on the Aβ(1–42) dimer, an Aβ(1–42) dimer based on monomeric the Aβ(1–42) peptide with enriched coil structures is constructed. The early molecular mechanisms of quercetin molecules on inhibiting the Aβ(1–42) dimer at two different Aβ42-to-quercetin molar ratios (1:5 and 1:10) are explored via all-atom molecular dynamics simulations. The results indicate that quercetin molecules can impede the configurational change of the Aβ(1–42) dimer. The interactions and the binding affinity between the Aβ(1–42) dimer and quercetin molecules in the Aβ42 dimer + 20 quercetin system are stronger in comparison with that in the Aβ42 dimer + 10 quercetin system. Our work may be helpful in developing new drug candidates for preventing the conformational transition and further aggregation of the Aβ dimer.