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Hydrodynamic effects on β-amyloid (16-22) peptide aggregation
The Journal of Chemical Physics ( IF 3.1 ) Pub Date : 2016-07-15 12:28:00 , DOI: 10.1063/1.4958323 Mara Chiricotto 1 , Simone Melchionna 2 , Philippe Derreumaux 1 , Fabio Sterpone 1
The Journal of Chemical Physics ( IF 3.1 ) Pub Date : 2016-07-15 12:28:00 , DOI: 10.1063/1.4958323 Mara Chiricotto 1 , Simone Melchionna 2 , Philippe Derreumaux 1 , Fabio Sterpone 1
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Computer simulations based on simplified representations are routinely used to explore the early steps of amyloid aggregation. However, when protein models with implicit solvent are employed, these simulations miss the effect of solvent induced correlations on the aggregation kinetics and lifetimes of metastable states. In this work, we apply the multi-scale Lattice Boltzmann Molecular Dynamics technique (LBMD) to investigate the initial aggregation phases of the amyloid Aβ 16−22 peptide. LBMD includes naturally hydrodynamic interactions (HIs) via a kinetic on-lattice representation of the fluid kinetics. The peptides are represented by the flexible OPEP coarse-grained force field. First, we have tuned the essential parameters that control the coupling between the molecular and fluid evolutions in order to reproduce the experimental diffusivity of elementary species. The method is then deployed to investigate the effect of HIs on the aggregation of 100 and 1000 Aβ 16−22 peptides. We show that HIs clearly impact the aggregation process and the fluctuations of the oligomer sizes by favouring the fusion and exchange dynamics of oligomers between aggregates. HIs also guide the growth of the leading largest cluster. For the 100 Aβ 16−22 peptide system, the simulation of ∼300 ns allowed us to observe the transition from ellipsoidal assemblies to an elongated and slightly twisted aggregate involving almost the totality of the peptides. For the 1000 Aβ 16−22 peptides, a system of unprecedented size at quasi-atomistic resolution, we were able to explore a branched disordered fibril-like structure that has never been described by other computer simulations, but has been observed experimentally.
中文翻译：
水动力对 β-淀粉样蛋白 (16-22) 肽聚集的影响
基于简化表示的计算机模拟通常用于探索淀粉样蛋白聚集的早期步骤。然而，当采用具有隐式溶剂的蛋白质模型时，这些模拟忽略了溶剂诱导的相关性对聚集动力学和亚稳态寿命的影响。在这项工作中，我们应用多尺度格子玻尔兹曼分子动力学技术（LBMD）来研究淀粉样蛋白 A β 16−22的初始聚集阶段肽。LBMD 通过流体动力学的动力学晶格表示包括自然流体动力相互作用 (HI)。肽由灵活的 OPEP 粗粒度力场表示。首先，我们调整了控制分子和流体演化之间耦合的基本参数，以便重现基本物质的实验扩散率。然后将该方法用于研究 HI 对 100 和 1000 个 A β 16−22肽聚集的影响。我们表明，HI 通过促进聚集体之间低聚物的融合和交换动态，明显影响聚集过程和低聚物尺寸的波动。HI 还引导领先的最大集群的增长。对于 100 A β 16−22在肽系统中，~300 ns 的模拟使我们能够观察到从椭圆体组装到几乎涉及整个肽的细长且稍微扭曲的聚集体的转变。对于 1000 个 A β 16−22肽，这是一个在准原子分辨率下规模空前的系统，我们能够探索一种分支无序原纤维样结构，这种结构从未被其他计算机模拟描述过，但已通过实验观察到。
更新日期：2016-07-16
中文翻译：
水动力对 β-淀粉样蛋白 (16-22) 肽聚集的影响
基于简化表示的计算机模拟通常用于探索淀粉样蛋白聚集的早期步骤。然而，当采用具有隐式溶剂的蛋白质模型时，这些模拟忽略了溶剂诱导的相关性对聚集动力学和亚稳态寿命的影响。在这项工作中，我们应用多尺度格子玻尔兹曼分子动力学技术（LBMD）来研究淀粉样蛋白 A β 16−22的初始聚集阶段肽。LBMD 通过流体动力学的动力学晶格表示包括自然流体动力相互作用 (HI)。肽由灵活的 OPEP 粗粒度力场表示。首先，我们调整了控制分子和流体演化之间耦合的基本参数，以便重现基本物质的实验扩散率。然后将该方法用于研究 HI 对 100 和 1000 个 A β 16−22肽聚集的影响。我们表明，HI 通过促进聚集体之间低聚物的融合和交换动态，明显影响聚集过程和低聚物尺寸的波动。HI 还引导领先的最大集群的增长。对于 100 A β 16−22在肽系统中，~300 ns 的模拟使我们能够观察到从椭圆体组装到几乎涉及整个肽的细长且稍微扭曲的聚集体的转变。对于 1000 个 A β 16−22肽，这是一个在准原子分辨率下规模空前的系统，我们能够探索一种分支无序原纤维样结构，这种结构从未被其他计算机模拟描述过，但已通过实验观察到。
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