Among the various factors controlling the amyloid aggregation process, the influences of ions on the aggregation rate and the resulting structures are important aspects to consider, which can be studied by molecular simulations. There is a wide variety of protein force fields and ion models, raising the question of which model to use in such studies. To address this question, we perform molecular dynamics simulations of Aβ_16–22, a fragment of the Alzheimer's amyloid β peptide, using different protein force fields, AMBER99SB-disp (A99-d) and CHARMM36m (C36m), and different ion parameters. The influences of NaCl and CaCl₂ at various concentrations are studied and compared with the systems without the addition of ions. Our results indicate a sensitivity of the peptide-ion interactions to the different ion models. In particular, we observe a strong binding of Ca²⁺ to residue E22 with C36m and also with the Åqvist ion model used together with A99-d, which slightly affects the monomeric Aβ_16–22 structures and the aggregation rate, but significantly affects the oligomer structures formed in the aggregation simulations. For example, at high Ca²⁺ concentrations, there was a switch from an antiparallel to a parallel β-sheet. Such ionic influences are of biological relevance because local ion concentrations can change in vivo and could help explain the polymorphism of amyloid fibrils.

中文翻译：

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离子类型和浓度对淀粉样肽 Aβ16−22$$ 的结构和聚集的影响 {\boldsymbol{\beta}}_{16-22} $$

在控制淀粉样蛋白聚集过程的各种因素中，离子对聚集速率和所得结构的影响是需要考虑的重要方面，可以通过分子模拟来研究。蛋白质力场和离子模型有很多种，这就提出了在此类研究中使用哪种模型的问题。为了解决这个问题，我们使用不同的蛋白质力场、AMBER99SB-disp (A99-d) 和 CHARMM36m (C36m) 以及不同的离子参数，对 A β _{16–22 （阿尔茨海默病淀粉样蛋白}β肽的片段）进行分子动力学模拟。_{研究了不同浓度的 NaCl 和 CaCl 2}的影响，并与不添加离子的体系进行了比较。我们的结果表明肽-离子相互作用对不同离子模型的敏感性。特别是，我们观察到 Ca ²⁺与残基 E22 与 C36m 以及与 A99-d 一起使用的 Åqvist 离子模型有很强的结合，这轻微影响单体 A β _16-22结构和聚集率，但显着影响聚集模拟中形成的低聚物结构。例如，在高 Ca ^{2+浓度下，存在从反平行到平行}β片层的转变。这种离子影响具有生物学相关性，因为局部离子浓度可以在体内发生变化，并且可以帮助解释淀粉样原纤维的多态性。