Using all-atom simulations in explicit solvent to study aggregation of amphipathic peptides into amyloid-like fibrils
Using all-atom simulations in explicit solvent to study aggregation of amphipathic peptides into amyloid-like fibrils
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DOI：
10.1016/j.molliq.2021.118283
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发表时间：
2022-02-01
影响因子：
6
通讯作者：
Dias, Cristiano
中科院分区：
文献类型：
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作者：
Jalali, Sharareh;Yang, Yanxing;Dias, Cristiano
在这里，我们在显式溶剂中进行全原子分子动力学模拟，以研究两亲性肽聚集成淀粉样蛋白原纤维。我们使用包含超过 200,000 个原子和 50 个肽的大型模拟盒来计算 30 mM 量级的肽浓度。这项工作研究了六种不同的肽序列。我们表明，当进行长时间模拟（2-3μs）时，实验和模拟之间观察到正相关。特别是，在实验中不形成原纤维的肽序列显示形成肽间氢键和β结构的倾向较低，反之亦然。还在不同温度和 NaCl 浓度下进行模拟，以强调疏水性和静电相互作用对聚集的重要性。在我们的模拟中，对于由高度疏水性氨基酸制成的两亲性肽，原纤维形成的速率随着温度的升高而增加。这种现象与随着温度升高而增强的疏水相互作用的强度有关。静电相互作用可能是我们模拟中偏向反平行β-折叠的原因。然而，筛选这些与 NaCl 的相互作用有利于由疏水性较低的氨基酸制成的两亲性肽的聚集。还讨论了我们的模拟中导致原纤维生长的事件顺序。 (C) 2021 Elsevier B.V. 保留所有权利。
Here, we perform all-atom molecular dynamics simulations in explicit solvent to study the aggregation of amphipathic peptides into amyloid-like fibrils. We use large simulation boxes containing more than 200,000 atoms and including 50 peptides to account for peptide concentrations of the order of 30 mM. Six different peptide sequences are studied in this work. We show that when long simulations (2-3 mu s) are performed, a positive correlation is observed between experiments and simulations. In particular, peptide sequences that do not form fibrils in experiments show a low propensity to form inter-peptide hydrogen bonds and beta-structures, and vice versa. Simulations are also performed at different temperatures and NaCl concentration to highlight the importance of hydrophobic and electrostatic interactions on aggregation. The rate of fibril formation in our simulations increases with increasing temperature for amphipathic peptides made from highly hydrophobic amino acids. This phenomena is related to the strength of hydrophobic interactions that enhances with increasing temperature. Electrostatic interactions may be responsible for the preference of anti-parallel beta-sheets in our simulations. However, screening these interactions with NaCl favors aggregation of amphipathic peptides made from less hydrophobic amino acids. The sequence of events leading to fibril growth in our simulations is also discussed. (C) 2021 Elsevier B.V. All rights reserved.