Peptide‐protein docking is challenging due to the considerable conformational freedom of the peptide. CAPRI rounds 38‐45 included two peptide‐protein interactions, both characterized by a peptide forming an additional beta strand of a beta sheet in the receptor. Using the Rosetta FlexPepDock peptide docking protocol we generated top‐performing, high‐accuracy models for targets 134 and 135, involving an interaction between a peptide derived from L‐MAG with DLC8. In addition, we were able to generate the only medium‐accuracy models for a particularly challenging target, T121. In contrast to the classical peptide‐mediated interaction, in which receptor side chains contact both peptide backbone and side chains, beta‐sheet complementation involves a major contribution to binding by hydrogen bonds between main chain atoms. To establish how binding affinity and specificity are established in this special class of peptide‐protein interactions, we extracted PeptiDBeta , a benchmark of solved structures of different protein domains that are bound by peptides via beta‐sheet complementation, and tested our protocol for global peptide‐docking PIPER‐FlexPepDock on this dataset. We find that the beta‐strand part of the peptide is sufficient to generate approximate and even high resolution models of many interactions, but inclusion of adjacent motif residues often provides additional information necessary to achieve high resolution model quality.

中文翻译：

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β-折叠肽-蛋白质相互作用建模：CAPRI 第 38-45 轮中的 Rosetta FlexPepDock。


由于肽具有相当大的构象自由度，肽-蛋白质对接具有挑战性。 CAPRI 第 38-45 轮包括两种肽-蛋白质相互作用，两者的特征都是肽在受体中形成 β 片层的额外 β 链。使用Rosetta FlexPepDock肽对接方案，我们为目标 134 和 135 生成了性能最佳的高精度模型，涉及 L-MAG 衍生的肽与 DLC8 之间的相互作用。此外，我们能够为特别具有挑战性的目标 T121 生成唯一的中等精度模型。与经典的肽介导的相互作用（其中受体侧链同时接触肽主链和侧链）相反，β-折叠互补对主链原子之间的氢键结合有重大贡献。为了确定在这种特殊类型的肽-蛋白质相互作用中如何建立结合亲和力和特异性，我们提取了PeptiDBeta ，这是通过 β-折叠互补与肽结合的不同蛋白质结构域的已解决结构的基准，并测试了我们的全局肽协议‐在此数据集上对接PIPER‐FlexPepDock 。我们发现肽的β链部分足以生成许多相互作用的近似甚至高分辨率模型，但包含相邻基序残基通常提供实现高分辨率模型质量所需的额外信息。