物理化学学报 >> 2011, Vol. 27 >> Issue (10): 2447-2456.doi: 10.3866/PKU.WHXB20111009

生物物理化学 上一篇    下一篇

SH3结构域序列集的统计耦联分析

徐海松, 李晓琴, 曾毅   

  1. 北京工业大学生命科学与生物工程学院, 北京 100124
  • 收稿日期:2011-04-19 修回日期:2011-07-26 发布日期:2011-09-27
  • 通讯作者: 李晓琴 E-mail:lxq0811@bjut.edu.cn
  • 基金资助:

    北京市自然科学基金(4092008, 4112010)资助项目

Statistical Coupling Analysis of a SH3 Domain Sequence Set

XU Hai-Song, LI Xiao-Qin, ZENG Yi   

  1. School of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, P. R. China
  • Received:2011-04-19 Revised:2011-07-26 Published:2011-09-27
  • Contact: LI Xiao-Qin E-mail:lxq0811@bjut.edu.cn
  • Supported by:

    The project was supported by the Beijing Municipal Natural Science Foundation, China (4092008, 4112010).

摘要: 基于蛋白质可折叠性和热稳定性具有长程相关性(即耦联性)的事实, 使用改进的统计耦联方法分析了SH3结构域序列集中存在的耦联性信息. 结果表明统计耦联方法采用的保守性统计能量可以较好地评估SH3结构域序列集的位点保守性, 具有高平均耦联能量的位点可以基本上对应一些结构或功能上具有重要意义的位点. 对统计耦联数据的一些位点扰动个案分析揭示出SH3 结构中包含非紧邻扰动和紧邻扰动模式. 统计耦联方法结合聚类重排可以对SH3折叠型序列群体中结构核心与非结构核心的位点进行区分, 甚至可以区分其中几个功能相关位点的细节差异. SH3结构域中包含了一系列的扰动模式, 不同的扰动模式涉及不同的位点组合; 各种扰动模式通过一些共有的扰动位点和扰动响应位点相互影响, 并最终决定结构中各位点的耦联响应模式. 这些耦联信息对于理解蛋白质的序列与结构和功能的关系, 以及设计新的蛋白序列有潜在价值.

关键词: 蛋白质功能, 蛋白质稳定性, 扰动模式, 耦联响应模式, 残基共进化

Abstract: Given the long range correlation characteristics of information about protein foldability and thermostability the multiple sequence alignment of a SH3 domain was analyzed using the modified statistical coupling analysis (SCA) method. Results show that the statistically conserved energy from the SCA method could be used to evaluate the site conservation of the SH3 sequence set properly. Sites with a high average coupling energy correspond to structurally and functionally important positions. Perturbing analysis on several sites revealed local and nonlocal perturbing modes in the SH3 domain. By combining the SCA and the clustering reorder method the structural core and the non-structural core sites of the SH3 domain, and detailed differences between several functional sites could be distinguished. Different perturbing modes that involve different sites exist in the SH3 domain. By sharing the common perturbing sites and the responding sites, different perturbing modes can interact. The coupling responding mode of all the sites in the structure was thus determined. Coupling information about the SH3 domain can improve our understanding about the relationship between the protein sequence and its structure as well as its function. It is also valuable in new protein design.

Key words: Protein function, Protein stability, Perturbing mode, Coupling responding mode, Residue coevolution

MSC2000: 

  • O641