Overington J, Donnelly D, Johnson M S, Sali A, Blundell T L
Department of Crystallography, Birkbeck College, University of London, UK.
Protein Sci. 1992 Feb;1(2):216-26. doi: 10.1002/pro.5560010203.
The local environment of an amino acid in a folded protein determines the acceptability of mutations at that position. In order to characterize and quantify these structural constraints, we have made a comparative analysis of families of homologous proteins. Residues in each structure are classified according to amino acid type, secondary structure, accessibility of the side chain, and existence of hydrogen bonds from the side chains. Analysis of the pattern of observed substitutions as a function of local environment shows that there are distinct patterns, especially for buried polar residues. The substitution data tables are available on diskette with Protein Science. Given the fold of a protein, one is able to predict sequences compatible with the fold (profiles or templates) and potentially to discriminate between a correctly folded and misfolded protein. Conversely, analysis of residue variation across a family of aligned sequences in terms of substitution profiles can allow prediction of secondary structure or tertiary environment.
折叠蛋白质中氨基酸的局部环境决定了该位置突变的可接受性。为了表征和量化这些结构限制，我们对同源蛋白质家族进行了比较分析。每个结构中的残基根据氨基酸类型、二级结构、侧链可及性以及侧链氢键的存在进行分类。对观察到的取代模式作为局部环境的函数进行分析表明，存在不同的模式，特别是对于埋藏的极性残基。取代数据表可随《蛋白质科学》一起在软盘上获取。给定蛋白质的折叠结构，就能够预测与该折叠结构兼容的序列（轮廓或模板），并有可能区分正确折叠和错误折叠的蛋白质。相反，根据取代轮廓分析比对序列家族中的残基变异可以预测二级结构或三级环境。
