Zhang Qian, Feng Ting, Xu Lei, Sun Huiyong, Pan Peichen, Li Youyong, Li Dan, Hou Tingjun
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Curr Drug Targets. 2016;17(14):1586-1594. doi: 10.2174/1389450117666160112112640.
Protein-protein interactions (PPIs) play important roles in a variety of biological processes, and many PPIs have been regarded as biologically compelling targets for drug discovery. Extensive efforts have been made to develop feasible proteinprotein docking approaches to study PPIs in silico. Most of these approaches are composed of two stages: sampling and scoring. Sampling is used to generate a number of plausible protein-protein binding conformations and scoring can rank all those conformations. Due to large and flexible binding interface of PPI, determination of the near native structures is computationally expensive, and therefore computational efficiency is the most challenging issue in protein-protein docking. Here, we have reviewed the basic concepts and implementations of the sampling, scoring and acceleration algorithms in some established docking programs, and the limitations of these algorithms have been discussed. Then, some suggestions to the future directions for sampling, scoring and acceleration algorithms have been proposed. This review is expected to provide a better understanding of protein-protein docking and give some clues for the optimization and improvement of available approaches.
蛋白质-蛋白质相互作用(PPIs)在多种生物学过程中发挥着重要作用,许多PPIs已被视为药物研发中具有生物学吸引力的靶点。人们已付出大量努力来开发可行的蛋白质-蛋白质对接方法,以便在计算机上研究PPIs。这些方法大多由两个阶段组成:采样和评分。采样用于生成大量合理的蛋白质-蛋白质结合构象,评分则可对所有这些构象进行排序。由于PPI的结合界面大且灵活,确定接近天然的结构在计算上成本高昂,因此计算效率是蛋白质-蛋白质对接中最具挑战性的问题。在此,我们回顾了一些已确立的对接程序中采样、评分和加速算法的基本概念及实现方式,并讨论了这些算法的局限性。然后,针对采样、评分和加速算法的未来发展方向提出了一些建议。本综述旨在更好地理解蛋白质-蛋白质对接,并为现有方法的优化和改进提供一些线索。