Ngo Son Tung, Truong Duc Toan, Tam Nguyen Minh, Nguyen Minh Tho
Computational Chemistry Research Group, Ton Duc Thang University, Ho Chi Minh City, Viet Nam; Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Viet Nam.
Computational Chemistry Research Group, Ton Duc Thang University, Ho Chi Minh City, Viet Nam; Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Viet Nam.
J Mol Graph Model. 2017 Sep;76:1-10. doi: 10.1016/j.jmgm.2017.06.018. Epub 2017 Jun 21.
An extensive replica exchange molecular dynamics (REMD) simulation was performed to investigate the progress patterns of the inhibition of (-)-epigallocatechin-3-gallate (EGCG) on the Aβ hexamer. Structural variations of the oligomers without and with EGCG were monitored and analyzed in detail. It has been found that EGCG prevents the formation of Aβ oligomer through two different ways by either accelerating the Aβ oligomerization or reducing the β-content of the hexamer. It also decreases the potential "highly toxic" conformations of Aβ oligomer, which is related to the conformations having high order β-sheet sizes. Both electrostatic and van der Waals interaction energies are found to be involved to the binding process. Computed results using quantum chemical methods show that the π-π stacking is a critical factor of the interaction between EGCG and the peptides. As a result, the binding free energy of the EGCG to the Aβ peptides is slightly larger than that of the curcumin.
进行了广泛的副本交换分子动力学（REMD）模拟，以研究（-）-表没食子儿茶素-3-没食子酸酯（EGCG）对Aβ六聚体抑制作用的进展模式。详细监测和分析了有无EGCG时寡聚体的结构变化。已发现EGCG通过加速Aβ寡聚化或降低六聚体的β含量这两种不同方式来阻止Aβ寡聚体的形成。它还降低了Aβ寡聚体潜在的“高毒性”构象，这与具有高阶β-折叠大小的构象有关。发现静电相互作用能和范德华相互作用能都参与了结合过程。使用量子化学方法的计算结果表明，π-π堆积是EGCG与肽之间相互作用的关键因素。结果，EGCG与Aβ肽的结合自由能略大于姜黄素与Aβ肽的结合自由能。
