In silico identification of functional protein interfaces
In silico identification of functional protein interfaces
复制标题
DOI：
10.1002/cfg.309
复制
发表时间：
2003-08-01
影响因子：
--
通讯作者：
Ben-Tal, N
中科院分区：
文献类型：
--
作者：
Bell, RE;Ben-Tal, N
蛋白质通过蛋白质-蛋白质、蛋白质-DNA 或蛋白质-配体界面发挥许多生物学作用。构成这些界面的氨基酸的鉴定通常可以增强我们对蛋白质生物学功能的理解。已经开发了许多用于检测功能接口的方法，并且大规模分析已经提供了对其准确性的评估。其中包括考虑蛋白质界面的大小、氨基酸组成及其物理化学和几何特性。达到此效果的其他方法使用成对相互作用的统计势函数和进化信息。进化方法的基本原理是功能和结构约束施加选择压力；因此，生物学上重要的界面的进化速度通常比蛋白质的其他外部区域慢。最近，我们的实验室开发了一种算法 Rate4Site 和网络服务器 ConSurf (http://consurf.tau.ac.il/)，用于根据系统发育树中反映的同源蛋白质之间的进化关系来识别功能接口。树拓扑和分支长度的显式使用使得该方法非常准确和灵敏。在这里，我们展示了它在识别假设蛋白质的功能界面方面的效力，该蛋白质的结构是作为国际结构基因组学工作的一部分而确定的。最后，我们建议结合互补程序，以提高蛋白质功能界面识别方法的整体性能。版权所有 (C) 2003 John Wiley Sons, Ltd.
Proteins perform many of their biological roles through protein-protein, protein-DNA or protein-ligand interfaces. The identification of the amino acids comprising these interfaces often enhances our understanding of the biological function of the proteins. Many methods for the detection of functional interfaces have been developed, and large-scale analyses have provided assessments of their accuracy. Among them are those that consider the size of the protein interface, its amino acid composition and its physicochemical and geometrical properties. Other methods to this effect use statistical potential functions of pairwise interactions, and evolutionary information. The rationale of the evolutionary approach is that functional and structural constraints impose selective pressure; hence, biologically important interfaces often evolve at a slower pace than do other external regions of the protein. Recently, an algorithm, Rate4Site, and a web-server, ConSurf (http://consurf.tau.ac.il/), for the identification of functional interfaces based on the evolutionary relations among homologous proteins as reflected in phylogenetic trees, were developed in our laboratory. The explicit use of the tree topology and branch lengths makes the method remarkably accurate and sensitive. Here we demonstrate its potency in the identification of the functional interfaces of a hypothetical protein, the structure of which was determined as part of the international structural genomics effort. Finally, we propose to combine complementary procedures, in order to enhance the overall performance of methods for the identification of functional interfaces in proteins.' Copyright (C) 2003 John Wiley Sons, Ltd.