There is experimental evidence that the astaxanthin, betanin and EGCG (epigallocatechin-3-gallate) compounds slow down the aggregation kinetics and the toxicity of the amyloid-beta (Aβ) peptide. How these inhibitors affect self-assembly at the atomic level remains elusive. To address this issue, we have performed for each ligand atomistic replica exchange molecular dynamics (REMD) simulations in explicit solvent of the Aβ11-40 trimer from the U-shape conformation, and MD simulations starting from Aβ1-40 dimer and tetramer structures characterized by different intra- and inter-peptide conformations. We find that the three ligands have similar binding free energies on small Aβ40 oligomers, but very distinct transient binding sites that will affect aggregation of larger assemblies and fibril elongation of Aβ40 peptide.

中文翻译：

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虾青素，甜菜碱和EGCG化合物对淀粉样蛋白Aβ40肽的小寡聚物的影响。

有实验证据表明虾青素，甜菜碱和EGCG（表没食子儿茶素-3-没食子酸酯）化合物减慢了淀粉样β（Aβ）肽的聚集动力学和毒性。这些抑制剂如何影响原子级的自组装仍然不清楚。为了解决这个问题，我们针对每个配体从U形构象在Aβ11-40三聚体的显式溶剂中进行了原子复制副本交换分子动力学（REMD）模拟，并从Aβ1-40二聚体和四聚体结构开始进行了MD模拟，其特征是不同的肽内和肽间构象。我们发现这三个配体在小的Aβ40寡聚物上具有相似的结合自由能，但是非常不同的瞬态结合位点会影响较大装配体的聚集和Aβ40肽的原纤维伸长。