Amphiphilic Peptides A6K and V6K Display Distinct Oligomeric Structures and Self-Assembly Dynamics: A Combined All-Atom and Coarse-Grained Simulation Study.
Amphiphilic Peptides A6K and V6K Display Distinct Oligomeric Structures and Self-Assembly Dynamics: A Combined All-Atom and Coarse-Grained Simulation Study.
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DOI：
10.1021/acs.biomac.5b00850
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发表时间：
2015-09
影响因子：
6.2
通讯作者：
Yunxiang Sun;Zhenyu Qian;Cong Guo;Guanghong Wei
中科院分区：
文献类型：
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作者：
Yunxiang Sun;Zhenyu Qian;Cong Guo;Guanghong Wei
两亲性多肽可以自组装成具有不同形貌的有序纳米结构。然而，组装机制和结构的早期组件之前，纳米结构的形成仍然难以捉摸。在这项研究中，我们研究了两个两亲性七肽A6 K和V6 K的寡聚体结构的全原子显式溶剂复制交换分子动力学（REMD）模拟，然后检查大聚集体的组装动力学粗粒度（CG）MD模拟。我们的200 ns REMD模拟表明，A6 K肽主要采用松散堆积的无序卷曲聚集体，而V6 K肽主要组装成紧凑的富含β-片层的构象，与在水溶液中实验测量的信号一致。组织良好的富含β-片层的构象，尽管具有低的群体，也被填充为V6 K八聚体，包括双层β-片层和β-桶。这些有序的富含β-片层的构象是首次在两亲性肽中观察到的。对200条肽链的10 μs CG-MD模拟结果表明，A6 K和V6 K多肽遵循两种不同的自组装过程，前者形成单层片层，后者组装成板状组装体。CG-MD模拟还表明，V6 K肽显示出比A6 K更高的组装能力，支持我们的全原子REMD模拟结果。肽间相互作用的分析表明，A6 K和V6 K之间的寡聚体结构和组装动力学的显着差异，从两个肽之间的疏水，氢键和静电相互作用的竞争的微妙的相互作用的结果。我们的研究为A6 K和V6 K在分子水平上的初始自组装过程提供了结构和机制上的见解。
Amphiphilic peptides can self-assemble into ordered nanostructures with different morphologies. However, the assembly mechanism and the structures of the early assemblies prior to nanostructure formation remain elusive. In this study, we investigated the oligomeric structures of two amphiphilic heptapeptides A6K and V6K by all-atom explicit-solvent replica-exchange molecular dynamics (REMD) simulations, and then examined the assembly dynamics of large aggregates by coarse-grained (CG) MD simulations. Our 200 ns REMD simulations show that A6K peptides predominantly adopt loosely packed disordered coil aggregates, whereas V6K peptides mostly assemble into compact β-sheet-rich conformations, consistent with the signal measured experimentally in aqueous solution. Well-organized β-sheet-rich conformations, albeit with low population, are also populated for V6K octamers, including bilayer β-sheets and β-barrels. These ordered β-sheet-rich conformations are observed for the first time for amphiphilic peptides. Our 10-μs CG-MD simulations on 200 peptide chains demonstrate that A6K and V6K peptides follow two different self-assembly processes, and the former form monolayer lamellas while the latter assemble into plate-like assemblies. CG-MD simulations also show that V6K peptides display higher assembly capability than A6K, in support of our all-atom REMD simulation results. Interpeptide interaction analyses reveal that the marked differences in oligomeric structures and assembly dynamics between A6K and V6K result from the subtle interplay of competition among hydrophobic, hydrogen-bonding, and electrostatic interactions of the two peptides. Our study provides structural and mechanistic insights into the initial self-assembly process of A6K and V6K at the molecular level.