Molecular insights into the inhibitory mechanisms of gallate moiety on the Aβ 1 - 40 amyloid aggregation: A molecular dynamics simulation study.

Autor: Nie RZ; School of Food Science and Technology, School of Chemical Engineering, Hubei University of Arts and Science, Xiangyang 441053, China; Food Ingredients Engineering Technology Research Center of Hubei, China., Huo YQ; School of Food Science and Technology, School of Chemical Engineering, Hubei University of Arts and Science, Xiangyang 441053, China; Food Ingredients Engineering Technology Research Center of Hubei, China., Yu B; School of Food Science and Technology, School of Chemical Engineering, Hubei University of Arts and Science, Xiangyang 441053, China; Food Ingredients Engineering Technology Research Center of Hubei, China., Liu CJ; School of Food Science and Technology, School of Chemical Engineering, Hubei University of Arts and Science, Xiangyang 441053, China; Food Ingredients Engineering Technology Research Center of Hubei, China., Zhou R; School of Food Science and Technology, School of Chemical Engineering, Hubei University of Arts and Science, Xiangyang 441053, China; Food Ingredients Engineering Technology Research Center of Hubei, China., Bao HH; School of Food Science and Technology, School of Chemical Engineering, Hubei University of Arts and Science, Xiangyang 441053, China; Food Ingredients Engineering Technology Research Center of Hubei, China., Tang SW; School of Food Science and Technology, School of Chemical Engineering, Hubei University of Arts and Science, Xiangyang 441053, China; Food Ingredients Engineering Technology Research Center of Hubei, China. Electronic address: shangwen_tang@163.com.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2020 Aug 01; Vol. 156, pp. 40-50. Date of Electronic Publication: 2020 Apr 08.
DOI: 10.1016/j.ijbiomac.2020.04.007
Abstrakt: 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.
Competing Interests: Declaration of competing interest There are no conflicts of interest to declare.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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