The mechanisms of flavonoids inhibiting conformational transition of amyloid- beta sub(42) monomer: a comparative molecular dynamics simulation study

• Published in: RSC advances Vol. 5; no. 81; pp. 66391 - 66402
• Main Authors: Wang, Ling, Zeng, Ranran, Pang, Xiaoqian, Gu, Qiong, Tan, Wen
• Format: Journal Article
• Language: English
• Published: 01.08.2015
• Subjects: Agglomeration; Design analysis; Flavonoids; Free energy; Inhibition; Molecular dynamics; Monomers; Simulation
• ISSN: 2046-2069
• DOI: 10.1039/c5ra12328c

Flavonoids can bind A beta sub(42) to inhibit the aggregation of A beta sub(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 silicoexperiments revealed that flavonoids halt the conformational transition of A beta sub(42) monomer by inhibiting beta -sheet formation; the flavonoids push the residues D23 and K28 of A beta sub(42) to be exposed to solvated water, destroy the salt bridge between D23 and K28, induce the conformational distribution of A beta sub(42) into local minimization energy conformational state, and generate U-shaped A beta sub(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 A beta sub(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 A beta sub(42) so as to treat Alzheimer's disease.