On the Applicability of Force Fields To Study the Aggregation of Amyloidogenic Peptides Using Molecular Dynamics Simulations
On the Applicability of Force Fields To Study the Aggregation of Amyloidogenic Peptides Using Molecular Dynamics Simulations
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DOI：
10.1021/acs.jctc.8b00579
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发表时间：
2018-11-01
影响因子：
5.5
通讯作者：
Strodel, Birgit
中科院分区：
文献类型：
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作者：
Carballo-Pacheco, Martin;Ismail, Ahmed E.;Strodel, Birgit
分子动力学模拟在理解生物分子过程中起着至关重要的作用，如蛋白质聚集在时间和空间分辨率，这是无法通过实验方法实现的。为了正确模拟蛋白质聚集，力场必须准确地表示分子间的相互作用。在这里，我们研究了五种不同力场对阿尔茨海默氏症A β（16-22）肽及其两种突变体的寡聚体形成的影响：A β（16-22）（F19 V，F20 V），它不形成原纤维，A β（16-22）（F19 L）形成原纤维比野生型更快。我们观察到，虽然低聚物形成动力学强烈依赖于力场，结构特性，如最相关的蛋白质-蛋白质接触，它们之间是相似的。不同的力场得到的寡聚体形成动力学的不同，彼此之间的聚集和非聚集肽用一个单一的力场模拟的动力学。我们讨论的困难，比较原子模拟的淀粉样蛋白低聚物的形成与实验观测。
Molecular dynamics simulations play an essential role in understanding biomolecular processes such as protein aggregation at temporal and spatial resolutions which are not attainable by experimental methods. For a correct modeling of protein aggregation, force fields must accurately represent molecular interactions. Here, we study the effect of five different force fields on the oligomer formation of Alzheimer's A beta(16-22) peptide and two of its mutants: A beta(16-22)(F19V,F20V), which does not form fibrils, and A beta(16-22)(F19L) which forms fibrils faster than the wild type. We observe that while oligomer formation kinetics depends strongly on the force field, structural properties, such as the most relevant protein-protein contacts, are similar between them. The oligomer formation kinetics obtained with different force fields differ more from each other than the kinetics between aggregating and nonaggregating peptides simulated with a single force field. We discuss the difficulties in comparing atomistic simulations of amyloid oligomer formation with experimental observables.