Extending RosettaDock with water, sugar, and pH for prediction of complex structures and affinities for CAPRI rounds 20-27.
Extending RosettaDock with water, sugar, and pH for prediction of complex structures and affinities for CAPRI rounds 20-27.
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DOI：
10.1002/prot.24425
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发表时间：
2013-12
影响因子：
2.9
通讯作者：
Gray, Jeffrey J.
中科院分区：
文献类型：
--
作者：
Kilambi, Krishna Praneeth;Pacella, Michael S.;Xu, Jianqing;Labonte, Jason W.;Porter, Justin R.;Muthu, Pravin;Drew, Kevin;Kuroda, Daisuke;Schueler-Furman, Ora;Bonneau, Richard;Gray, Jeffrey J.
第20-27轮前蛋白相互作用的关键评估（卡普里）为旨在解决广泛挑战的计算方法提供了测试平台。不同的目标推动了计算工具的创造和新的组合。在这项研究中，RosettaDock和其他新的Rosetta协议被用于成功预测10个盲靶中的4个。例如，对于Colicin E2-Im 2免疫蛋白的DNase结构域，使用RosettaDock和RosettaLigand预测水分子在界面处的位置，恢复了46%的天然水介导的接触。对于α-重复Rep 4-Rep 2和g-型溶菌酶-PliG抑制剂复合物，构建同源模型，并使用标准和pH敏感的对接算法生成界面RMSD值分别为3.3 μ g和2.0 μ g的结构。还开发了一种新的灵活的糖-蛋白质对接方案，并用于BT4661-肝素样糖复合物的结构预测，回收了71%的天然接触。挑战仍然存在于蛋白质突变体的精确同源性模型的生成和全球对接过程中的采样。在设计用于结合流感血凝素的蛋白质上，只有大约一半的突变被鉴定出影响结合（T55：54%; T56：48%）。涉及同源建模和多结构域对接的木聚糖酶复合物的结构的预测推动了全局构象采样的限制，并没有导致任何成功的预测。手头的问题的多样性需要计算算法是通用的，最近增加的罗塞塔套件扩展的能力，包括更多的生物现实的对接问题。
Rounds 20–27 of the Critical Assessment of PRotein Interactions (CAPRI) provided a testing platform for computational methods designed to address a wide range of challenges. The diverse targets drove the creation of and new combinations of computational tools. In this study, RosettaDock and other novel Rosetta protocols were used to successfully predict four of the 10 blind targets. For example, for DNase domain of Colicin E2–Im2 immunity protein, RosettaDock and RosettaLigand were used to predict the positions of water molecules at the interface, recovering 46% of the native water-mediated contacts. For α-repeat Rep4–Rep2 and g-type lysozyme–PliG inhibitor complexes, homology models were built and standard and pH-sensitive docking algorithms were used to generate structures with interface RMSD values of 3.3 Å and 2.0 Å, respectively. A novel flexible sugar–protein docking protocol was also developed and used for structure prediction of the BT4661–heparin-like saccharide complex, recovering 71% of the native contacts. Challenges remain in the generation of accurate homology models for protein mutants and sampling during global docking. On proteins designed to bind influenza hemagglutinin, only about half of the mutations were identified that affect binding (T55: 54%; T56: 48%). The prediction of the structure of the xylanase complex involving homology modeling and multidomain docking pushed the limits of global conformational sampling and did not result in any successful prediction. The diversity of problems at hand requires computational algorithms to be versatile; the recent additions to the Rosetta suite expand the capabilities to encompass more biologically realistic docking problems.
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影响因子：
2.9
作者：
ANDERSON, DE;BECKTEL, WJ;DAHLQUIST, FW
通讯作者：
DAHLQUIST, FW
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：
2.9
作者：
Chaudhury, Sidhartha;Sircar, Aroop;Gray, Jeffrey J.
通讯作者：
Gray, Jeffrey J.
影响因子：
5.6
作者：
Gray, JJ;Moughon, S;Baker, D
通讯作者：
Baker, D
影响因子：
5.6
作者：
Chaudhury, Sidhartha;Gray, Jeffrey J.
通讯作者：
Gray, Jeffrey J.