PIIMS Server: A Web Server for Mutation Hotspot Scanning at the Protein-Protein Interface
PIIMS Server: A Web Server for Mutation Hotspot Scanning at the Protein-Protein Interface
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PIIMS 服务器：用于蛋白质-蛋白质界面突变热点扫描的 Web 服务器
DOI：
10.1021/acs.jcim.0c00966
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发表时间：
2021-01-05
影响因子：
5.6
通讯作者：
Yang, Guang-Fu
中科院分区：
文献类型：
--
作者：
Wu, Feng-Xu;Yang, Jing-Fang;Yang, Guang-Fu
蛋白质相互作用(PPI)在调节细胞和信号通路等生物过程中起着至关重要的作用。热点是位于蛋白质-蛋白质界面的某些残基，与其他残基相比，对蛋白质-蛋白质结合的贡献更大。研究热点的突变效应对于理解蛋白质结合的基本方面是很重要的。因此，已经开发了各种计算工具来探索突变热点的影响，这将使人们能够更好地理解驱动PPI的力量。然而，可以在热点地区提供全面替代的工具仍然很少。因此，迫切需要一种新的免费Web服务器来探索热点的突变影响。在这里，我们介绍了一个集成了分子动力学模拟和一步自由能微扰的Web服务器PIIMS。它包含两个主要的计算功能：(1)计算丙氨酸扫描分析以识别热点；(2)全突变扫描分析以评估热点突变的影响。我们严格验证了它预测结合自由能变化的能力，通过使用大量和多样化的数据集，包括来自50个PPI的1341个突变，相关系数R=0.75。与现有工具的不同之处在于，PIIMS可以针对它们的不同突变对热点残基进行进一步评估。PIIMS网络服务器(可在http://chemyang.ccnu.edu.cn/ccb/server/PIIMS/index.php)is免费访问，无需登录即可向所有用户开放)。
Protein-protein interactions (PPIs) play vital roles in regulating biological processes, such as cellular and signaling pathways. Hotspots are certain residues located at protein-protein interfaces that contribute more in protein-protein binding than other residues. Research on the mutational effects of hotspots is important for understanding basic aspects of protein association. Hence, various computational tools have been developed to explore the impact of mutation hotspots, which will allow a better understanding of the forces that drive PPIs. However, tools that may provide comprehensive substitutions at hotspots are still rare. Hence, there is a strong need for a new free web server to explore mutational effects of hotspots. Herein we introduce a web server named PIIMS that integrates molecular dynamics simulation and one-step free energy perturbation. It contains two main computational functions: (1) computational alanine scanning analysis to identify hotspots and (2) full mutation scanning analysis to evaluate the effects of hotspot mutations. We rigidly validated its ability to predict binding free energy changes by using large and diverse datasets including 1,341 mutations from 50 PPIs with the correlation coefficient R = 0.75. The difference from the existing tools is that PIIMS can perform further evaluation of hotspot residues with regard to their different mutations. The PIIMS web server (accessible at http://chemyang.ccnu.edu.cn/ccb/server/PIIMS/index.php)is free and open to all users without login requirements.