Docking protein domains in contact space.
Docking protein domains in contact space.
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DOI：
10.1186/1471-2105-7-310
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发表时间：
2006-06-21
影响因子：
3
通讯作者：
Jones DT
中科院分区：
文献类型：
--
作者：
Lise S;Walker-Taylor A;Jones DT
许多生物学过程涉及蛋白质结构域之间的物理相互作用。理解这些功能性关联需要分子结构的知识。实验研究虽然提出了相当大的困难，因此需要准确和可靠的计算方法。在本文中，我们提出了一种新的方法，旨在对接蛋白质结构域使用接触图表示。该方法不是提供复合物的完整三维模型，而是预测跨界面的接触残基。我们使用的评分功能，结合结构，物理化学和进化信息，其中每个潜在的残基接触被分配一个值，根据评分功能和假设是接触的真实的配置是一个最大化的分数。直接在接触空间中用模拟退火算法进行搜索。我们已经测试了相互作用的结构域对，是同一蛋白质（分子内结构域）的一部分的方法。我们表明，它正确地预测一些接触，预测的残基往往是显着更接近对方比其他对残基在同一个域。此外，我们发现，预测的接触往往可以区分最好的模型（或原生结构，如果存在的话）之间的一组最佳解决方案产生的标准对接程序。接触对接似乎是可行的，并能够补充其他计算方法预测蛋白质-蛋白质相互作用。相对于更标准的对接算法，它可能更适合于处理蛋白质构象变化和预测从蛋白质模型开始的复合物。
Many biological processes involve the physical interaction between protein domains. Understanding these functional associations requires knowledge of the molecular structure. Experimental investigations though present considerable difficulties and there is therefore a need for accurate and reliable computational methods. In this paper we present a novel method that seeks to dock protein domains using a contact map representation. Rather than providing a full three dimensional model of the complex, the method predicts contacting residues across the interface. We use a scoring function that combines structural, physicochemical and evolutionary information, where each potential residue contact is assigned a value according to the scoring function and the hypothesis is that the real configuration of contacts is the one that maximizes the score. The search is performed with a simulated annealing algorithm directly in contact space. We have tested the method on interacting domain pairs that are part of the same protein (intra-molecular domains). We show that it correctly predicts some contacts and that predicted residues tend to be significantly closer to each other than other pairs of residues in the same domains. Moreover we find that predicted contacts can often discriminate the best model (or the native structure, if present) among a set of optimal solutions generated by a standard docking procedure. Contact docking appears feasible and able to complement other computational methods for the prediction of protein-protein interactions. With respect to more standard docking algorithms it might be more suitable to handle protein conformational changes and to predict complexes starting from protein models.
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