Approaches to predicting effects of single amino acid substitutions on the function of a protein.
Approaches to predicting effects of single amino acid substitutions on the function of a protein.
复制标题
预测单个氨基酸取代对蛋白质功能影响的方法。
DOI：
10.1021/bi00239a022
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发表时间：
1991
期刊：
影响因子：
2.9
通讯作者：
Terwilliger,TC
中科院分区：
文献类型：
--
作者：
Zabin,HB;Horvath,MP;Terwilliger,TC
芝加哥大学生物化学与分子生物学系，伊利诺伊州芝加哥市东58街920号，邮编60637摘要：利用噬菌体fl基因V蛋白313个突变体的体内相对活性测定，对预测单氨基酸取代对蛋白质功能影响的两种方法进行了评价。首先，我们测试了只依赖于野生型和替代氨基酸性质的方法。我们测试的氨基酸的性质或功能等效性的测量，包括同源蛋白之间氨基酸交换的频率以及侧链大小、疏水性和电荷的变化，都没有发现与突变体的活性有太弱的相关性。发现这种差相关性的主要原因是特定替代的效果在不同位点之间差异很大。然后，我们测试了一种方法，使用几个突变体在一个位点上的替换来预测另一个突变体的活性，我们发现这是一个相对较好的指标，表明该位点上的另一个突变体是否会起作用。建立了一种预测方案，该方案结合了依赖于野生型和取代氨基酸性质的模型的弱信息和来自位点对取代的耐受性的强信息。虽然这种方案不需要了解突变蛋白的结构，但它在预测突变蛋白的活性方面是有用的。
Department of Biochemistry and Molecular Biology, The University of Chicago, 920 East 58th Street, Chicago, Illinois 60637 Received September 18, 1990; Revised Manuscript Received January 11, 1991 abstract: The relative activities of 313 mutants of the gene V protein of bacteriophage fl, assayed in vivo, have been used to evaluate two approaches to predicting the effects of single amino acid substitutions on the function of a protein. First, we tested methods that only depend on the properties of the wild-type and substituting amino acids. None of the properties or measures of the functional equivalence of amino acids we tested, including the frequency of exchange of amino acids among homologous proteins as well as changes in side-chain size, hydrophobicity, and charge, were found to be more than weakly correlated with the activities of mutants. The principal reason for this poor correlation was found to be that the effect of a particular substitution varies considerably from siteto site. We thentested an approach using the activities of several mutants with substitutions at a site to predict the activity of another mutant, and we find that this is a relatively good indicator of whether the other mutant at that site will be functional. A predictive scheme was developed that combines the weak information from the models depending on the properties of the wild-type and substituting amino acids with the stronger information from the tolerance of a site to substitution. Although this scheme requires no knowledge of the structure of a mutant protein, it is useful in predicting the activities of mutants.