Structural assembly of two-domain proteins by rigid-body docking.
Structural assembly of two-domain proteins by rigid-body docking.
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DOI：
10.1186/1471-2105-9-441
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发表时间：
2008-10-16
影响因子：
3
通讯作者：
Fernandez-Recio J
中科院分区：
文献类型：
--
作者：
Cheng TM;Blundell TL;Fernandez-Recio J
具有多个结构域的蛋白质建模是结构生物学的核心挑战之一。虽然同源性建模已成功地应用于蛋白质结构的预测，但通常不能从同源物的结构推断结构域-结构域相互作用，并且它们的预测需要从头算方法。在这里，我们提出了一个新的结构预测方法建模的两个结构域的蛋白质的基础上刚体域对接。在这里，我们专注于相互作用的结构域对，它们是同一肽链的一部分，因此具有结构域间肽区域（所谓的接头）。我们已经开发了一种称为pyDockTET（拴系对接）的方法，它使用刚体对接生成域域的姿势，进一步得分的结合能和伪能量项的基础上来自连接器端到端的距离的限制。该方法已被基准上的一组77个非冗余对可用的X射线结构的域。我们已经评估了对接方法ZDOCK，这是能够产生可接受的域域方向在51的77例。其中，我们的方法pyDockTET在超过60%的情况下在前10个解决方案中找到了正确的组装。作为进一步的测试，在通过同源性建模构建的20对结构域的子集上，ZDOCK在20种情况中的13种情况下生成可接受的方向，其中通过我们的pyDockTET方法，在大约70%的情况下，正确的组装排名低于10。我们的研究结果表明，刚体对接的方法加上能量评分和基于链接的约束是有用的建模域域之间的相互作用。这些积极的结果将鼓励发展新的方法，结构预测的大分子与多个（两个以上）域。
Modelling proteins with multiple domains is one of the central challenges in Structural Biology. Although homology modelling has successfully been applied for prediction of protein structures, very often domain-domain interactions cannot be inferred from the structures of homologues and their prediction requires ab initio methods. Here we present a new structural prediction approach for modelling two-domain proteins based on rigid-body domain-domain docking. Here we focus on interacting domain pairs that are part of the same peptide chain and thus have an inter-domain peptide region (so called linker). We have developed a method called pyDockTET (tethered-docking), which uses rigid-body docking to generate domain-domain poses that are further scored by binding energy and a pseudo-energy term based on restraints derived from linker end-to-end distances. The method has been benchmarked on a set of 77 non-redundant pairs of domains with available X-ray structure. We have evaluated the docking method ZDOCK, which is able to generate acceptable domain-domain orientations in 51 out of the 77 cases. Among them, our method pyDockTET finds the correct assembly within the top 10 solutions in over 60% of the cases. As a further test, on a subset of 20 pairs where domains were built by homology modelling, ZDOCK generates acceptable orientations in 13 out of the 20 cases, among which the correct assembly is ranked lower than 10 in around 70% of the cases by our pyDockTET method. Our results show that rigid-body docking approach plus energy scoring and linker-based restraints are useful for modelling domain-domain interactions. These positive results will encourage development of new methods for structural prediction of macromolecules with multiple (more than two) domains.
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Pfam：氏族、网络工具和服务。
影响因子：
14.9
作者：
Finn, Robert D.;Mistry, Jaina;Schuster-Bockler, Benjamin;Griffiths-Jones, Sam;Hollich, Volker;Lassmann, Timo;Moxon, Simon;Marshall, Mhairi;Khanna, Ajay;Durbin, Richard;Eddy, Sean R.;Sonnhammer, Erik L. L.;Bateman, Alex
通讯作者：
Bateman, Alex
影响因子：
2.9
作者：
Ben-Zeev, E;Kowalsman, N;Eisenstein, M
通讯作者：
Eisenstein, M
影响因子：
5.6
作者：
ARGOS, P
通讯作者：
ARGOS, P
影响因子：
3
作者：
Lise S;Walker-Taylor A;Jones DT
通讯作者：
Jones DT
影响因子：
2
作者：
Inbar, Y;Benyamini, H;Wolfson, HJ
通讯作者：
Wolfson, HJ