Modeling beta-sheet peptide-protein interactions: Rosetta FlexPepDock in CAPRI rounds 38-45.
Modeling beta-sheet peptide-protein interactions: Rosetta FlexPepDock in CAPRI rounds 38-45.
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DOI：
10.1002/prot.25871
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发表时间：
2020-08
期刊：
影响因子：
2.9
通讯作者：
Schueler-Furman O
中科院分区：
文献类型：
--
作者：
Khramushin A;Marcu O;Alam N;Shimony O;Padhorny D;Brini E;Dill KA;Vajda S;Kozakov D;Schueler-Furman O
由于肽的相当大构象自由，肽蛋白对接很具有挑战性。 Capri回合38-45包括两种肽 - 蛋白质相互作用，均以肽在受体中形成β板的额外β链。使用Rosetta Flexpepdock肽对接协议，我们为目标134和135生成了表现最佳的高准确模型，涉及从L-MAG与DLC8得出的肽之间的相互作用。此外，我们能够为一个特别具有挑战性的目标T121生成唯一的中等准确模型。与经典肽介导的相互作用相比，受体侧链接触肽骨架和侧链，β-片互补涉及对主链原子之间氢键结合的重大贡献。为了确定在这种特殊类别的肽 - 蛋白质相互作用中如何建立结合亲和力和特异性，我们提取了肽贝塔，这是通过β- - 此数据集上的docking 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，但是包含相邻的基序残基通常会提供实现高分辨率模型质量所需的其他信息。
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.
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影响因子：
14.8
作者：
Kozakov D;Hall DR;Xia B;Porter KA;Padhorny D;Yueh C;Beglov D;Vajda S
通讯作者：
Vajda S
DOI：
10.1007/978-1-4939-7000-1_26
发表时间：
2017
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Burley SK;Berman HM;Kleywegt GJ;Markley JL;Nakamura H;Velankar S
通讯作者：
Velankar S
影响因子：
3.3
作者：
Barlow, Kyle A.;Conchuir, Shane O.;Kortemme, Tanja
通讯作者：
Kortemme, Tanja
DOI：
10.1073/pnas.1200678109
发表时间：
2012-06-12
影响因子：
11.1
作者：
Kundrotas, Petras J.;Zhu, Zhengwei;Vakser, Ilya A.
通讯作者：
Vakser, Ilya A.
影响因子：
8
作者：
Frappier, Vincent;Duran, Madeleine;Keating, Amy E.
通讯作者：
Keating, Amy E.