基于去折叠自由能的蛋白质结构域划分方法——适用于连续与不连续结构域  

A Method for Delineation of Domains in Proteins Based on Refolding Free Energy ——Application to Continuous and Discontinuous Domains

作　　者：谢志群[1] 许根俊[1] 

机构地区：[1]中国科学院上海生命科学研究院生物化学与细胞生物学研究所,上海200031

出　　处：《生物化学与生物物理学报》2003年第12期1090-1098,共9页

基　　金：国家自然科学基金项目资助 (No .3 993 0 0 60 )~~

摘　　要：结构域是蛋白质的一个结构层次 ,可以看作是蛋白质结构、折叠、功能、进化和设计的基本单位。大多数的蛋白质都可分为若干个结构域 ,结构域的不同组合使蛋白质具有不同的三级结构并具有不同的功能。蛋白质结构域的划分在理论与应用上都具有重要意义 ,但目前对结构域的划分还没有一个十分理想的方法。作者曾经发展了一种通过计算去折叠自由能划分蛋白质结构域的方法 ,但该方法只适用于连续双结构域的划分。现在 ,作者通过构造氨基酸残基相互作用矩阵 ,并进行对应分析 (correspondenceanalysis) ,然后根据去折叠自由能和一些经验打分函数对蛋白质进行切割和优选 ,发展了可以同时处理连续和不连续结构域的划分方法。该方法与晶体结构作者手工分析相比较 ,二者的结果有 76 %的相似。Domain is a protein architecture in a subunit. It might be defined as a basic unit for structure, function, folding, evolution and design. Different combinations of domains lead to the formation of various tertiary structures with various functions for proteins. The delineation of domains for a protein is important both conceptually and practically, which remains up to date a challenging and unsolved problem. Based on the above definition, a method was previously proposed based on refolding free energy to define continuous domains in proteins. By constructing a residue-residue contact matrix, using correspondence analysis, and then selecting optimal partition function of a protein according to refolding free energy and some empirical scoring functions, a new computer program, PDOM, was developed, which was applicable to both continuous and discontinuous domains. When compared with the manual partition results reported by crystallographers, PDOM has achieved an accuracy of 76% on a test data set including 55 protein structures frequently used. The differences in 13 proteins between PDOM, literature as well as SCOP have been discussed extensively.

关 键 词：结构域 划分 自由能 作用矩阵 蛋白质 肽链 

分 类 号：Q51[生物学—生物化学]