Overington J, Johnson M S, Sali A, Blundell T L
Department of Crystallography, Birkbeck College, University of London, U.K.
Proc Biol Sci. 1990 Aug 22;241(1301):132-45. doi: 10.1098/rspb.1990.0077.
The pattern of residue substitution in divergently evolving families of globular proteins is highly variable. At each position in a fold there are constraints on the identities of amino acids from both the three-dimensional structure and the function of the protein. To characterize and quantify the structural constraints, we have made a comparative analysis of families of homologous globular proteins. Residues are classified according to amino acid type, secondary structure, accessibility of the sidechain, and existence of hydrogen bonds from sidechain to other sidechains or peptide carbonyl or amide functions. There are distinct patterns of substitution especially where residues are both solvent inaccessible and hydrogen bonded through their sidechains. The patterns of residue substitution can be used to construct templates or to identify 'key' residues if one or more structures are known. Conversely, analysis of conversation and substitution across a large family of aligned sequences in terms of substitution profiles can allow prediction of tertiary environment or indicate a functional role. Similar analyses can be used to test the validity of putative structures if several homologous sequences are available.
球状蛋白质趋异进化家族中残基取代的模式高度可变。在一个折叠结构的每个位置，蛋白质的三维结构和功能对氨基酸的特性都有一定限制。为了表征和量化这些结构限制，我们对同源球状蛋白质家族进行了比较分析。残基根据氨基酸类型、二级结构、侧链的可及性以及侧链与其他侧链或肽羰基或酰胺官能团之间氢键的存在情况进行分类。存在明显的取代模式，特别是在残基既不可与溶剂接触又通过其侧链形成氢键的地方。如果已知一个或多个结构，残基取代模式可用于构建模板或识别“关键”残基。相反，根据取代谱分析一大组比对序列中的保守性和取代情况，可以预测三级结构环境或表明其功能作用。如果有几个同源序列，类似的分析可用于检验假定结构的有效性。
