The rational design of linear peptides that assemble controllably and predictably in water is challenging. Sequences must encode unique target structures and avoid alternative states. However, the stabilizing and discriminating non-covalent forces available are weak in water. Nonetheless, for α-helical coiled-coil assemblies considerable progress has been made in rational de novo design. In these, sequence repeats of nominally hydrophobic (h) and polar (p) residues, hpphppp, direct the assembly of amphipathic helices into dimeric to tetrameric bundles. Expanding this pattern to hpphhph can produce larger α-helical barrels. Here, we show that pentamers to nonamers are achieved simply by vary-ing the residue at one of these h sites. In L/I-K-E-I-A-x-Z repeats, decreasing the size of Z from threonine to serine to ala-nine to glycine gives progressively larger oligomers. X-ray crystal structures of the resulting α-helical barrels rationalize this: side chains at Z point directly into the helical interfaces, and smaller residues allow closer helix contacts and larger assemblies.

中文翻译：

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盘绕线圈9到5：具有可调低聚物状态的α螺旋桶的从头设计

在水中可控和可预测地组装的线性肽的合理设计具有挑战性。序列必须编码独特的目标结构，并避免其他状态。但是，在水中可用的稳定和区分非共价力很弱。尽管如此，对于α-螺旋线圈组件，在合理的从头设计中已经取得了相当大的进步。在这些中，标称疏水残基（h）和极性残基（p）的重复序列hpphppp将两亲性螺旋组装成二聚体至四聚体束。将此模式扩展为hpphhph可以产生更大的α螺旋桶。在这里，我们表明，仅通过改变这些h个位点之一上的残基即可实现五聚体至九聚体。在L / IKEIAxZ重复中，从苏氨酸到丝氨酸到丙氨酸到甘氨酸减小Z的大小会得到越来越大的低聚物。所得的α螺旋桶的X射线晶体结构对此进行了合理化处理：Z侧链直接指向螺旋界面，较小的残基允许更紧密的螺旋接触和更大的组装。