Different nanostructures caused by competition of intra- and inter-β-sheet interactions in hierarchical self-assembly of short peptides
Different nanostructures caused by competition of intra- and inter-β-sheet interactions in hierarchical self-assembly of short peptides
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DOI：
10.1016/j.jcis.2015.11.030
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发表时间：
2016-02-15
影响因子：
9.9
通讯作者：
Xu, Hai
中科院分区：
文献类型：
--
作者：
Zhou, Peng;Deng, Li;Xu, Hai
为了了解分子间的相互作用如何导致扭曲、螺旋和扁平纳米带的自组装，我们通过实验和分子动力学（MD）模拟比较了三种具有相同氨基酸组成但不同序列的八肽的分级自组装过程。KE-F8（NH 2-KFEFKE-CONH 2）和EK-F8（NH 2-KFEFKE-CONH 2）具有相同的疏水残基分布，并且仅通过交换其C-末端的带正电荷和负电荷的残基而不同，而KFE-8（NH 2-KFEFKFEF-CONH 2）与KE-F8和EK-F8的不同之处在于具有均匀分布的所有疏水和带电荷的残基。分子动力学模拟结果表明，分子水平上静电和疏水相互作用的竞争导致了不同的初始堆积模式：KE-F8单体形成完全匹配的反平行f1-折叠，EK-F8单体以一个残基移位排列，KFE-8单体以两个异质表面堆积β-折叠，这与先前提出的模型一致。在链间和片间相互作用的驱动下，这些分子模板的进一步生长导致具有不同扭曲和堆叠程度的更大的低聚物，这与实验观察到的自组装形态在结构上是一致的。进一步的MD模拟表明，β-折叠内和β-折叠间相互作用之间的竞争是导致β-折叠的不同扭曲和堆叠程度以及随后形成不同纳米结构（KE-F8的扭曲带，EK-F8的螺旋带/管和KFE-8的扁平带）的原因。因此，这项研究提供了一个重要的机制洞察微调的分子包装和相互作用，通过肽序列的变化，导致可控的自组装扭曲，螺旋和平面纳米结构。(C)由Elsevier Inc.出版。
To understand how molecular interactions lead to the self-assembly of twisted, helical and flat nanoribbons, we have compared the hierarchical self-assembly processes of three selected octapeptides with the same amino acid composition but different sequences by both experiments and molecular dynamics (MD) simulations. KE-F8 (NH2-KEFFFFKE-CONH2) and EK-F8 (NH2-KEFFFFEK-CONH2) have the same distribution of hydrophobic residues and only differ by swapping the positive and negative charged residues at their C-terminals, while KFE-8 (NH2-KFEFKFEF-CONH2) differs from KE-F8 and EK-F8 by having all hydrophobic and charged residues evenly distributed. MD simulations indicated that the competition between electrostatic and hydrophobic interactions at the molecular level results in different initial packing modes: KE-F8 monomers form completely matched anti-parallel fl-sheets, EK-F8 monomers align with one residue shifting, and KFE-8 monomers pack beta-sheets with two heterogeneous surfaces, consistent with previously suggested models. Driven by inter-strand and inter-sheet interactions, further growth of these molecular templates leads to larger oligomers with different twisting and stacking degrees, which are structurally consistent with the experimentally observed self-assembled morphologies. Further MD simulations showed that the competition between intra-beta-sheet and inter-beta-sheet interactions is responsible for the different twisting and stacking degrees of beta-sheets and the subsequent formation of different nanostructures (twisted ribbons for KE-F8, helical ribbons/tubes for EK-F8 and flat ribbons for KFE-8). This study thus provided an important mechanistic insight into the fine tuning of molecular packing and interactions via peptide sequence variation leading to controllable self-assembly of twisted, helical and flat nanostructures. (C) 2015 Published by Elsevier Inc.