Structural modeling of protein complexes: Current capabilities and challenges
Structural modeling of protein complexes: Current capabilities and challenges
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DOI：
10.1002/prot.25774
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发表时间：
2019-07-22
影响因子：
2.9
通讯作者：
Venclovas, Ceslovas
中科院分区：
文献类型：
--
作者：
Dapkunas, Justas;Olechnovic, Kliment;Venclovas, Ceslovas
蛋白质经常相互作用，并且必须了解相应蛋白质复合物的结构以了解它们的功能。计算方法越来越多地用于提供蛋白质复合物的结构模型。毫不奇怪，蛋白质结构预测（CASP）实验的社区范围内的批判性评估最近开始监测该研究领域的进度。我们参加了CASP13，目的是评估我们当前在蛋白质复合物建模的能力，并更好地了解对这些能力影响最大影响的因素。为了建模CASP13中的蛋白质复合物，我们应用了基于模板的建模，免费对接和混合技术，从而使我们能够生成42个多组中27个最高质量的模型。如果可以确定蛋白质复合物的模板，我们通过直接的同源性建模以合理的精度对结构进行建模。如果只有部分模板可用，则可以正确预测相互作用界面，或通过将基于模板的建模与docking相结合，从而为蛋白质复合物生成可接受的模型。如果没有模板可用，我们使用了刚体对接的成功有限。但是，在一些自由对接模型中，尽管子单位方向不正确和界面触点，但正确地识别了蛋白质结合位点的近似位置。显然，我们在扩展坞中的总体表现受单体模型的质量以及评分方法的不完美限制。人类干预对我们对蛋白质复合物建模的结果的影响很大，这表明需要改善自动方法。
Proteins frequently interact with each other, and the knowledge of structures of the corresponding protein complexes is necessary to understand how they function. Computational methods are increasingly used to provide structural models of protein complexes. Not surprisingly, community-wide Critical Assessment of protein Structure Prediction (CASP) experiments have recently started monitoring the progress in this research area. We participated in CASP13 with the aim to evaluate our current capabilities in modeling of protein complexes and to gain a better understanding of factors that exert the largest impact on these capabilities. To model protein complexes in CASP13, we applied template-based modeling, free docking and hybrid techniques that enabled us to generate models of the topmost quality for 27 of 42 multimers. If templates for protein complexes could be identified, we modeled the structures with reasonable accuracy by straightforward homology modeling. If only partial templates were available, it was nevertheless possible to predict the interaction interfaces correctly or to generate acceptable models for protein complexes by combining template-based modeling with docking. If no templates were available, we used rigid-body docking with limited success. However, in some free docking models, despite the incorrect subunit orientation and missed interface contacts, the approximate location of protein binding sites was identified correctly. Apparently, our overall performance in docking was limited by the quality of monomer models and by the imperfection of scoring methods. The impact of human intervention on our results in modeling of protein complexes was significant indicating the need for improvements of automatic methods.