iScore: a novel graph kernel-based function for scoring protein-protein docking models
iScore: a novel graph kernel-based function for scoring protein-protein docking models
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DOI：
10.1093/bioinformatics/btz496
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发表时间：
2020-01-01
期刊：
影响因子：
5.8
通讯作者：
Xue, Li C.
中科院分区：
文献类型：
--
作者：
Geng, Cunliang;Jung, Yong;Xue, Li C.
蛋白质复合物在生物学功能的许多方面发挥着关键作用。蛋白质复合物的三维（3D）结构对于深入了解相互作用的结构基础及其在协调关键细胞过程的生物分子途径中的作用至关重要。由于与3D蛋白质复合物结构的实验测定相关的费用和努力，计算对接已经发展为预测生物分子复合物的3D结构的有价值的工具。尽管最近的进展，可靠区分近本地对接构象从大量的候选conformations，所谓的评分问题，仍然是一个重大的challenge.Results在这里，我们提出iScore，一种新的方法来评分对接的构象，结合HADDOCK能量项与得分使用的蛋白质-蛋白质界面的图形表示和进化保守的措施。它在两个独立的数据集上实现了与最先进的评分函数竞争或上级的评分性能：（i）对接软件特定模型和（ii）由各种对接方法（即对接软件非特定）生成的卡普里评分集。与卡普里中的37个评分组相比，iScore在卡普里评分集（13个目标）中排名最高。结果表明，结合进化，拓扑和充满活力的信息得分对接构象的效用。这项工作代表了第一次成功的演示图内核的蛋白质接口的近天然和非天然构象的蛋白质复合物的有效地区分。可用性和实施iScore代码是免费提供的Github：https://github.com/DeepRank/iScore（DOI：10.5281/zenodo.2630567）。所用的对接模型可从SBGrid获得：https：//data.sbgrid.org/dataet/684）。补充信息补充数据可在生物信息学在线获得。
Motivation Protein complexes play critical roles in many aspects of biological functions. Three-dimensional (3D) structures of protein complexes are critical for gaining insights into structural bases of interactions and their roles in the biomolecular pathways that orchestrate key cellular processes. Because of the expense and effort associated with experimental determinations of 3D protein complex structures, computational docking has evolved as a valuable tool to predict 3D structures of biomolecular complexes. Despite recent progress, reliably distinguishing near-native docking conformations from a large number of candidate conformations, the so-called scoring problem, remains a major challenge.Results Here we present iScore, a novel approach to scoring docked conformations that combines HADDOCK energy terms with a score obtained using a graph representation of the protein-protein interfaces and a measure of evolutionary conservation. It achieves a scoring performance competitive with, or superior to, that of state-of-the-art scoring functions on two independent datasets: (i) Docking software-specific models and (ii) the CAPRI score set generated by a wide variety of docking approaches (i.e. docking software-non-specific). iScore ranks among the top scoring approaches on the CAPRI score set (13 targets) when compared with the 37 scoring groups in CAPRI. The results demonstrate the utility of combining evolutionary, topological and energetic information for scoring docked conformations. This work represents the first successful demonstration of graph kernels to protein interfaces for effective discrimination of near-native and non-native conformations of protein complexes.Availability and implementation The iScore code is freely available from Github: https://github.com/DeepRank/iScore (DOI: 10.5281/zenodo.2630567). And the docking models used are available from SBGrid: https://data.sbgrid.org/dataset/684).Supplementary informationSupplementary data are available at Bioinformatics online.