Templates are available to model nearly all complexes of structurally characterized proteins
Templates are available to model nearly all complexes of structurally characterized proteins
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DOI：
10.1073/pnas.1200678109
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发表时间：
2012-06-12
影响因子：
11.1
通讯作者：
Vakser, Ilya A.
中科院分区：
文献类型：
--
作者：
Kundrotas, Petras J.;Zhu, Zhengwei;Vakser, Ilya A.
传统的蛋白质 - 蛋白质对接样品样品的结合模式，无需考虑类似的实验确定的蛋白质 - 蛋白质复合物的结构（模板）。基于新兴模板的对接方法利用这种相似的复合物来确定对接预测。对接问题假设参与蛋白质的结构的知识。因此，它提供了对齐蛋白质和模板复合物的结构的可能性。基于模板的对接的开发和基于模板的单个蛋白质建模的丰富经验的进展表明，通常，这种方法比自由建模更可靠。该建模范式的关键方面是模板的可用性。当前的共同看法是，由于蛋白质 - 蛋白质复合物的实验结构确定的困难，对接模板的库池微不足道，因此只有在未来的某个时间才有可能的基于模板的对接的广泛应用。我们的大规模系统研究结果表明，尽管蛋白质数据库中蛋白质蛋白质复合物数量有限，但可以找到代表几乎所有已知蛋白质蛋白质相互作用的复合物，但可以找到对接模板，但前提是组件本身具有已知的结构，也可以是同源的。将模板与从蛋白质数据库中提取的测试集中的实验结构进行比较时，大约有三分之一的模板是良好的，并且在建模复合物时将是有用的起点。这一发现极大地扩展了我们建模蛋白质相互作用的能力，并且对蛋白质对接场具有深远的影响。
Traditional approaches to protein-protein docking sample the binding modes with no regard to similar experimentally determined structures (templates) of protein-protein complexes. Emerging template-based docking approaches utilize such similar complexes to determine the docking predictions. The docking problem assumes the knowledge of the participating proteins' structures. Thus, it provides the possibility of aligning the structures of the proteins and the template complexes. The progress in the development of template-based docking and the vast experience in template-based modeling of individual proteins show that, generally, such approaches are more reliable than the free modeling. The key aspect of this modeling paradigm is the availability of the templates. The current common perception is that due to the difficulties in experimental structure determination of protein-protein complexes, the pool of docking templates is insignificant, and thus a broad application of template-based docking is possible only at some future time. The results of our large scale, systematic study show that, surprisingly, in spite of the limited number of protein-protein complexes in the Protein Data Bank, docking templates can be found for complexes representing almost all the known protein-protein interactions, provided the components themselves have a known structure or can be homology-built. About one-third of the templates are of good quality when they are compared to experimental structures in test sets extracted from the Protein Data Bank and would be useful starting points in modeling the complexes. This finding dramatically expands our ability to model protein interactions, and has far-reaching implications for the protein docking field in general.