Interaction of A β 1 − 42 chains and fibrillary seeds studied by all-atom molecular dynamics simulations

IF 0.9 Q3 MATHEMATICS, APPLIED

Computational and Mathematical Methods Pub Date : 2020-11-24 DOI:10.1002/cmm4.1138

Lyudmyla Dorosh, Min Wu, Maria Stepanova

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引用次数: 1

Abstract

We apply all-atom molecular dynamics simulations to investigate interactions of amyloid beta (A $β$ ) fibril seeds with natively disordered A $β$ chains, a process associated with the onset of Alzheimer's disease. The simulations captured attachment of A $β$ chains to the fibrils suggesting an onset of both fibril's elongation and secondary nucleation, with a stronger affinity of attachment leading to elongation. Choice of fibril's model appears important for the propensity to recruit A $β$ chains from solution and retain them adsorbed. Nuclear magnetic resonance-based and cryo-electron microscopy derived models of A $β$ fibrils exhibited significant differences in the interaction with individual A $β$ chains, as well as in structural and dynamical stability in solution.

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全原子分子动力学模拟研究A β 1−42链与原纤维种子的相互作用

我们应用全原子分子动力学模拟来研究淀粉样蛋白β (A β)原纤维种子与天然紊乱的A β链的相互作用，这一过程与阿尔茨海默病的发病有关。模拟捕获了A β链与原纤维的连接，表明原纤维的延伸和二次成核同时开始，并且连接的亲和力更强，导致了延伸。纤维模型的选择对于从溶液中招募A β链并保持它们的吸附倾向很重要。基于核磁共振和低温电镜的A β原纤维模型在与单个A β链的相互作用以及在溶液中的结构和动力学稳定性方面存在显著差异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Computational and Mathematical Methods

CiteScore

2.20

自引率

0.00%

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