Molecular Simulations for Anti-amyloidogenic Effect of Flavonoid Myricetin Exerted against Alzheimer¡¯s ¥â-Amyloid Fibrils Formation

Bulletin of the Korean chemical society

Karpjoo Jeong¹  Seung R. Paik¹  Youngjin Choi¹  Seunho Jung¹  Thomas Donghyun Kim¹ 

关键词: Amyloid fibril;    Conformational analysis;    Flavonoid;    Molecular dynamics simulations;    Myricetin;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

Comparative molecular simulations were performed to establish molecular interaction and inhibitory effect of flavonoid myricetin on formation of amyloid fibris. For computational comparison, the conformational stability of myricetin with amyloid �?-peptide (A�?) and �?-amyloid fibrils (fA�?) were traced with multiple molecular dynamics simulations (MD) using the CHARMM program from Monte Carlo docked structures. Simulations showed that the inhibition by myricetin involves binding of the flavonoid to fA�? rather than A�?. Even in MD simulations over 5 ns at 300 K, myricetin/fA�? complex remained stable in compact conformation for multiple trajectories. In contrast, myricetin/A�? complex mostly turned into the dissociated conformation during the MD simulations at 300 K. These multiple MD simulations provide a theoretical basis for the higher inhibitory effect of myricetin on fibrillogenesis of fA�? relative to A�? . Significant binding between myricetin and fA�? observed from the computational simulations clearly reflects the previous experimental results in which only fA�? had bound to the myricetin molecules.

【 授权许可】

Unknown