Structure and stability of short β-peptide nanotubes:: A non-natural representative of collagen?
Structure and stability of short β-peptide nanotubes:: A non-natural representative of collagen?
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DOI：
10.1021/jp7114803
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发表时间：
2008-07-03
影响因子：
3.3
通讯作者：
Perczelt, Andras
中科院分区：
文献类型：
--
作者：
Czajlik, Andras;Beke, Tamas;Perczelt, Andras
由于已知二级结构元件在稳定蛋白质的3D折叠以设计由β-氨基酸残基组成的非天然蛋白质中起关键作用，因此必须构建合适的二级结构元件。已经描述了β-多肽的α-螺旋和P-链的折叠类似物（Chem. Biodiversity 2004，1，11111）。在这里，我们提出了几个胶原样褶皱完全由β-丙氨酸（S）。与它们的天然对应物不同，这些管状纳米结构可以由三个以上平行和/或反平行排列的多肽链组成。通过从头算和密度泛函理论计算，我们优化了大量的通用胶原样反平行纳米结构。在这些管状系统中，寡肽链通过i ->（i）型H键相互连接，除了“闭合”组。后者被称为“氢键拉链”，并且是（i）-> i、（i + 1）-> i或（i + 2）-> i类型。反平行的管状折叠体由I条链组成，每条链有k个P-氨基酸残基（例如，ap（β-T-i+1（1））（k）、ap（β-T-i+1（1））（k）或ap（β-T-i+2（1））（k））是出乎意料地稳定的超分子复合物。与k和l无关，氨基酸残基的局部骨架折叠通常是螺旋形的，缩写为“SP”或“S*p”。然而，与平行相反，在反平行纳米管中，骨架折叠偶尔会从Sp或S*p型扭曲成另一种局部结构。然而，股线的局部几何形状越类似于Sp或S*p，稳定性越高。除了骨架扭曲外，整体稳定性还取决于组成氢键的类型和几何性质。有趣的是，当氢键参数较差时，较高的总氢键数量可以提供较低的总体稳定性。一般来说，链的数目和它们的长度的增加稳定了超分子复合物。现在，对于P-肽，确定了胶原样整体折叠及其稳定性，必须揭示其POG或PPG样序列特异性。
Since secondary structure elements are known to play a key role in stabilizing the 3D-fold of proteins for the design of non-natural proteins composed of beta-amino acid residues, the construction of suitable secondary structural elements is mandatory. Folding analogues of alpha-helices and P-strands of beta-polypeptides were already described (Chem. Biodiversity 2004, 1, 11111). Here, we present several collagen-like folds composed exclusively of beta-Ala(s). Unlike their natural counterpart, these tubular nanostructures can be composed of more than three polypeptide chains aligned parallel and/or antiparallel. By using ab initio and DFT calculations we have optimized a large number of versatile collagen-like antiparallel nanostructures. In these tubular systems, oligopeptide strands are interconnected by i -> (i) type H-bonds, except for the "closing" set. This latter is called "the H-bond zipper" and is either (i) -> i, (i + 1) -> i, or (i + 2) -> i type. Antiparallel, tubular foldamers composed of I number of strands, each of k number of P-amino acid residues (e.g., ap(beta-T-i+l(l))(k), ap(beta-T-i+1(l))(k), or ap(beta-T-i+2(l))(k)) are unexpectedly stable supramolecular complexes. Independent of k and l, the local backbone fold of the amino acid residues is usually spiral, abbreviated as "SP" or "S*p". Nevertheless, in contrast to parallel, in antiparallel nanotubes the backbone fold can occasionally twist out from Sp or S*p type into an alternative local structure. However, the more the local geometry of the strands resembles to Sp or S*p, the higher the stability is. Besides the backbone twisting, the overall stability is determined by the type and the geometrical properties of the constituent H-bonds. Interestingly, higher number of total H-bonds can provide a lower overall stability, when H-bond parameters are inferior. In general, the increase of both the number of strands and their length stabilize the supramolecular complex. Now that, for P-peptides, collagenlike overall folds with their stability were determined, their POG- or PPG-like sequence specificity has to be revealed.