부산대학교 도서관

Alzheimer's disease is the most common form of neurodegenerative disease and the formation of Aβ amyloid aggregates has been widely demonstrated to be the principal cause of Alzheimer's disease. Our previous study and other studies suggested that the gallate moiety played an obligatory role in the inhibition process of naturally occurring polyphenols on Aβ amyloid fibrils formation. However, the detailed mechanisms were still unknown. Thus, in the present study, the gallic acid (GA) was specially selected and the molecular recognition mechanisms between GA molecules and Aβ 1 – 40 monomer were examined and analyzed by molecular dynamics simulation. The in silico experiments revealed that GA significantly prevented the conformational changes of Aβ 1 – 40 monomer with no β-sheet structure during the whole 100 ns. By analyzing the binding sites of GA molecules to Aβ 1 – 40 monomer, we found that both hydrophilic and hydrophobic amino acid residues were participated in the binding of GA molecules to Aβ 1 – 40 monomer. Moreover, results from the binding free energy analysis further demonstrated that the strength of polar interactions was significantly stronger than that of nonpolar interactions. We believed that our results could help to elucidate the underlying mechanisms of gallate moiety on the anti-amyloidogenic effects of polyphenols at the atomic level. • The mechanisms of gallate moiety on the anti-amyloidogenic effects of polyphenols were studied by MD simulation. • The conformation of Aβ 1-40 monomer in the presence of GA was less compact than that of Aβ 1-40 monomer alone. • The binding of GA to Aβ 1-40 monomer dramatically prevented the secondary structure transition from helix to β-sheet. • GA inhibited the long-range intra-Aβ 1-40 peptide sidechain-sidechain contacts. • The polar and nonpolar interactions were both involved in the binding of GA to Aβ 1-40 monomer. [ABSTRACT FROM AUTHOR]