Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.
Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.
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DOI：
10.1371/journal.pone.0018934
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发表时间：
2011-04-29
期刊：
影响因子：
3.7
通讯作者：
Schueler-Furman O
中科院分区：
文献类型：
--
作者：
Raveh B;London N;Zimmerman L;Schueler-Furman O
与另一种蛋白质分子结合后折叠的柔性多肽在活细胞中介导了大量的调节相互作用，并可能提供高度特异的识别模块。我们提出了Rosetta FlexPepDock ab-Initio，一种用于多肽同时对接和从头折叠的协议，从多肽结合位点的大致说明开始。利用Rosetta片段库和多肽和受体的粗粒度结构表示，FlexPepDock ab-Initio高效且同时地在给定结合位点的受体表面上采样可能的多肽骨架构象和刚体取向的空间。随后对粗粒度模型的全原子精化包括对受体和多肽的全侧链建模，从而得到高分辨率的模型，其中概括了关键的侧链相互作用。该方案被应用于一个基准测试，在该基准测试中，多肽以其结合的主干构象或以其自由、未结合的形式在受体上建模。18/26的结合病例和7/14的非结合病例发现了近天然的多肽构象。该协议对来自不同类别二级结构的多肽，包括具有不寻常转折和扭结的卷曲多肽，执行得很好。本文提出的结果极大地扩展了最先进的高分辨率多肽建模方法的范围，这些方法现在可以应用于各种多肽-蛋白质相互作用，在这些相互作用中，没有关于多肽骨架构象的先验信息，从而能够进行基于结构的详细研究和对这些相互作用的操纵。
Flexible peptides that fold upon binding to another protein molecule mediate a large number of regulatory interactions in the living cell and may provide highly specific recognition modules. We present Rosetta FlexPepDock ab-initio, a protocol for simultaneous docking and de-novo folding of peptides, starting from an approximate specification of the peptide binding site. Using the Rosetta fragments library and a coarse-grained structural representation of the peptide and the receptor, FlexPepDock ab-initio samples efficiently and simultaneously the space of possible peptide backbone conformations and rigid-body orientations over the receptor surface of a given binding site. The subsequent all-atom refinement of the coarse-grained models includes full side-chain modeling of both the receptor and the peptide, resulting in high-resolution models in which key side-chain interactions are recapitulated. The protocol was applied to a benchmark in which peptides were modeled over receptors in either their bound backbone conformations or in their free, unbound form. Near-native peptide conformations were identified in 18/26 of the bound cases and 7/14 of the unbound cases. The protocol performs well on peptides from various classes of secondary structures, including coiled peptides with unusual turns and kinks. The results presented here significantly extend the scope of state-of-the-art methods for high-resolution peptide modeling, which can now be applied to a wide variety of peptide-protein interactions where no prior information about the peptide backbone conformation is available, enabling detailed structure-based studies and manipulation of those interactions.
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通过计算机淘选对 α-突触核蛋白聚集调节剂进行肽配体筛选。
影响因子：
3
作者：
Abe, Koichi;Kobayashi, Natsuki;Sode, Koji;Ikebukuro, Kazunori
通讯作者：
Ikebukuro, Kazunori
影响因子：
6.8
作者：
Gai, S. Annie;Wittrup, K. Dane
通讯作者：
Wittrup, K. Dane
DOI：
10.1002/prot.340230412
发表时间：
1995-12-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Frishman, D;Argos, P
通讯作者：
Argos, P
影响因子：
5.6
作者：
Dutta S;Gullá S;Chen TS;Fire E;Grant RA;Keating AE
通讯作者：
Keating AE
DOI：
10.1073/pnas.97.19.10383
发表时间：
2000-09-12
影响因子：
11.1
作者：
Kuhlman, B;Baker, D
通讯作者：
Baker, D