VORFFIP-Driven Dock: V-D2OCK, a Fast and Accurate Protein Docking Strategy

The experimental determination of the structure of protein complexes cannot keep pace with the generation of interactomic data, hence resulting in an ever-expanding gap. As the structural details of protein complexes are central to a full understanding of the function and dynamics of the cell machinery, alternative strategies are needed to circumvent the bottleneck in structure determination. Computational protein docking is a valid and valuable approach to model the structure of protein complexes. In this work, we describe a novel computational strategy to predict the structure of protein complexes based on data-driven docking: VORFFIP-driven dock (V-D2OCK). This new approach makes use of our newly described method to predict functional sites in protein structures, VORFFIP, to define the region to be sampled during docking and structural clustering to reduce the number of models to be examined by users. V-D2OCK has been benchmarked using a validated and diverse set of protein complexes and compared to a state-of-art docking method. The speed and accuracy compared to contemporary tools justifies the potential use of VD2OCK for high-throughput, genome-wide, protein docking. Finally, we have developed a web interface that allows users to browser and visualize V-D2OCK predictions from the convenience of their web-browsers.蛋白质复合物结构的实验测定速率已难以跟上相互作用组数据的产出速率，由此导致二者间的缺口不断扩大。由于蛋白质复合物的结构细节是全面理解细胞机器功能与动态的核心所在，亟需探索其他策略以突破结构测定的瓶颈。计算蛋白质对接是模拟蛋白质复合物结构的有效且极具价值的途径。本研究提出了一种基于数据驱动对接的新型计算策略：VORFFIP驱动对接（V-D2OCK）。该方法依托我们新近开发的用于预测蛋白质结构功能位点的工具VORFFIP，划定对接过程中的采样区域，并通过结构聚类减少用户需审查的模型数量。我们采用经过验证且多样性丰富的蛋白质复合物数据集对V-D2OCK进行了基准测试，并将其与当前前沿的对接方法进行对比。相较于当代同类工具，V-D2OCK在速度与精度上的优势证明其可适用于高通量、全基因组规模的蛋白质对接任务。最后，我们开发了网页交互界面，用户可通过浏览器便捷地浏览并可视化V-D2OCK的预测结果。