Role of structural and sequence information in the prediction of protein stability changes: comparison between buried and partially buried mutations
Role of structural and sequence information in the prediction of protein stability changes: comparison between buried and partially buried mutations
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DOI：
10.1093/protein/12.7.549
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发表时间：
1999-07-01
期刊：
影响因子：
--
通讯作者：
Sarai, A
中科院分区：
文献类型：
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作者：
Gromiha, MM;Oobatake, M;Sarai, A
预测突变引起的蛋白质稳定性变化是分子生物学中最大的挑战之一，在这项工作中，我们分析了由埋藏突变和部分埋藏突变引起的稳定性变化与48种物理化学、能量和构象性质变化之间的相关性。我们发现反映疏水性的性质与埋藏突变的稳定性密切相关，并且性质值与碳原子数之间存在直接关系。根据突变在螺旋、链、转或线圈片段中的位置对其进行分类，提高了突变与稳定性的相关性。与α -螺旋片段的突变相比，β -链片段内的埋藏突变相关性更好，这表明β -链的疏水性更强。在有序结构（螺旋、链和转）中，部分埋藏突变引起的稳定性变化相关性最强，主要受疏水性控制。由于线圈的无序性，其稳定性变化机制与其他二级结构不同，线圈内部突变引起的稳定性变化主要受熵效应的影响。根据它们的氢键形成能力对线圈内的突变进行进一步分类，导致了更强的相关性。疏水性是决定埋藏突变稳定性的主要因素，而氢键、其他极性相互作用和疏水相互作用都是部分埋藏突变稳定性的重要决定因素。局部序列和结构效应信息对部分埋藏突变引起的稳定性变化的预测比埋藏突变更重要；他们将所有数据集的相关性平均提高了27%。
Predicting mutation-induced changes in protein stability is one of the greatest challenges in molecular biology, In this work, we analyzed the correlation between stability changes caused by buried and partially buried mutations and changes in 48 physicochemical, energetic and conformational properties. We found that properties reflecting hydrophobicity strongly correlated with stability of buried mutations, and there was a direct relation between the property values and the number of carbon atoms. Classification of mutations based on their location within helix, strand, turn or coil segments improved the correlation of mutations with stability. Buried mutations within beta-strand segments correlated better than did those in alpha-helical segments, suggesting stronger hydrophobicity of the beta-strands. The stability changes caused by partially buried mutations in ordered structures (helix, strand and turn) correlated most strongly and were mainly governed by hydrophobicity, Due to the disordered nature of coils, the mechanism underlying their stability differed from that of the other secondary structures: the stability changes due to mutations within the coil were mainly influenced by the effects of entropy. Further classification of mutations within coils, based on their hydrogen-bond forming capability, led to much stronger correlations. Hydrophobicity was the major factor in determining the stability of buried mutations, whereas hydrogen bonds, other polar interactions and hydrophobic interactions were all important determinants of the stability of partially buried mutations. Information about local sequence and structural effects were more important for the prediction of stability changes caused by partially buried mutations than for buried mutations; they strengthened correlations by an average of 27% among all data sets.