Center for Computational Biology and Bioinformatics and College of Engineering, Koc University Rumelifeneri Yolu, 34450 Sariyer Istanbul, Turkey;
Mol Cell Proteomics. 2014 Mar;13(3):887-96. doi: 10.1074/mcp.M113.031294. Epub 2014 Jan 20.
Most (if not all) proteins function when associated in multimolecular assemblies. Attaining the structures of protein assemblies at the atomic scale is an important aim of structural biology. Experimentally, structures are increasingly available, and computations can help bridge the resolution gap between high- and low-resolution scales. Existing computational methods have made substantial progress toward this aim; however, current approaches are still limited. Some involve manual adjustment of experimental data; some are automated docking methods, which are computationally expensive and not applicable to large-scale proteome studies; and still others exploit the symmetry of the complexes and thus are not applicable to nonsymmetrical complexes. Our study aims to take steps toward overcoming these limitations. We have developed a strategy for the construction of protein assemblies computationally based on binary interactions predicted by a motif-based protein interaction prediction tool, PRISM (Protein Interactions by Structural Matching). Previously, we have shown its power in predicting pairwise interactions. Here we take a step toward multimolecular assemblies, reflecting the more prevalent cellular scenarios. With this method we are able to construct homo-/hetero-complexes and symmetric/asymmetric complexes without a limitation on the number of components. The method considers conformational changes and is applicable to large-scale studies. We also exploit electron microscopy density maps to select a solution from among the predictions. Here we present the method, illustrate its results, and highlight its current limitations.
大多数（如果不是全部）蛋白质在多分子组装中发挥功能。在原子尺度上获得蛋白质组装的结构是结构生物学的一个重要目标。实验上，结构越来越多地可用，并且计算可以帮助弥合高分辨率和低分辨率之间的分辨率差距。现有的计算方法在实现这一目标方面已经取得了重大进展；然而，目前的方法仍然有限。一些方法涉及对实验数据的手动调整；一些是自动化对接方法，计算成本高，不适用于大规模蛋白质组研究；还有一些利用复合物的对称性，因此不适用于非对称复合物。我们的研究旨在克服这些限制。我们已经开发了一种基于基于基序的蛋白质相互作用预测工具 PRISM（通过结构匹配的蛋白质相互作用预测）预测的二进制相互作用的计算方法来构建蛋白质组装。以前，我们已经展示了它在预测成对相互作用方面的强大功能。在这里，我们朝着多分子组装迈出了一步，反映了更常见的细胞场景。通过这种方法，我们能够构建同/异源复合物以及对称/不对称复合物，而不受组件数量的限制。该方法考虑构象变化，适用于大规模研究。我们还利用电子显微镜密度图从预测中选择一个解决方案。在这里，我们介绍了该方法，说明了其结果，并强调了其当前的局限性。
