Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
Proteins. 2019 Dec;87(12):1222-1232. doi: 10.1002/prot.25774. Epub 2019 Jul 22.
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.
蛋白质经常相互作用，了解它们的功能需要知道相应蛋白质复合物的结构知识。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，最近的蛋白质结构预测（CASP）实验已经开始监测该研究领域的进展。我们参加了 CASP13，旨在评估我们在蛋白质复合物建模方面的现有能力，并更好地了解对这些能力影响最大的因素。为了在 CASP13 中对蛋白质复合物进行建模，我们应用了基于模板的建模、自由对接和混合技术，这些技术使我们能够为 42 个多聚体中的 27 个生成最高质量的模型。如果可以识别蛋白质复合物的模板，我们可以通过直接同源建模以合理的精度来模拟结构。如果只有部分模板可用，那么通过将基于模板的建模与对接相结合，仍然可以正确预测相互作用界面或生成蛋白质复合物的可接受模型。如果没有模板可用，则使用刚体对接的效果有限。然而，在一些自由对接模型中，尽管亚基方向不正确且接口接触丢失，但仍可以正确识别蛋白质结合位点的大致位置。显然，我们在对接方面的整体性能受到单体模型的质量和评分方法的不完善的限制。人为干预对我们在蛋白质复合物建模中的结果的影响是显著的，表明需要改进自动方法。
