The mechanisms of flavonoids inhibiting conformational transition of amyloid-β42 monomer: a comparative molecular dynamics simulation studyElectronic supplementary information (ESI) available. See DOI: 10.1039/c5ra12328c

• Main Authors: Wang, Ling, Zeng, Ranran, Pang, Xiaoqian, Gu, Qiong, Tan, Wen
• Format: Journal Article
• Language: English
• Published: 06.08.2015
• ISSN: 2046-2069
• DOI: 10.1039/c5ra12328c

Flavonoids can bind Aβ 42 to inhibit the aggregation of Aβ 42 monomer. However, the inhibitory mechanism remains unknown. Herein, comparable molecular dynamics simulations for a total of 710 ns were performed to study its mechanism. The in silico experiments revealed that flavonoids halt the conformational transition of Aβ 42 monomer by inhibiting β-sheet formation; the flavonoids push the residues D23 and K28 of Aβ 42 to be exposed to solvated water, destroy the salt bridge between D23 and K28, induce the conformational distribution of Aβ 42 into local minimization energy conformational state, and generate U-shaped Aβ 42 configurations, which have more stable helixes and fewer unstable random coils. Moreover, simulation results from the free energy landscape and binding free energy analyses suggest that biflavonoids are superior to monoflavonoids in inhibiting conformational transition of Aβ 42 monomer. These findings agree with the experimental data and may help in the design of new agents that will inhibit the conformational transition of Aβ 42 so as to treat Alzheimer's disease. Flavonoids can bind Aβ 42 to inhibit the aggregation of Aβ 42 monomer.