Importance of surrounding residues for protein stability of partially buried mutations
Importance of surrounding residues for protein stability of partially buried mutations
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DOI：
10.1080/07391102.2000.10506666
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发表时间：
2000-10-01
影响因子：
4.4
通讯作者：
Sarai, A
中科院分区：
文献类型：
--
作者：
Gromiha, MM;Oobatake, M;Sarai, A
为了了解影响蛋白质稳定性的因素，我们分析了由部分掩埋突变引起的蛋白质稳定性变化与48个氨基酸残基的物理化学、能量和构象性质变化之间的关系。本文推导了多元回归方程来预测蛋白质突变体的稳定性，并通过回测和折刀检验验证了该方法的有效性。我们观察到一个很好的协议之间的实验和计算的稳定性。此外，我们已经分析了突变残基每侧上1至12个残基的序列窗口长度的影响，以包括用于预测蛋白质稳定性的序列信息，并且我们发现对于每个二级结构，用于获得最高相关性的优选窗口长度是不同的;螺旋、链和卷曲突变的优选窗口长度分别是突变残基两侧的0、9和4个残基。然而，所有的二级结构具有显着的相关性的窗口长度的一个残基的每一侧的突变位置，这意味着短程相互作用的作用。提取突变体位置周围不同距离（3至20埃）的周围残基信息，分别在8埃、6埃和7埃处显示螺旋、链和卷曲片段突变的最高相关性。总体而言，关于7至8埃范围内的周围残基的信息可以更好地解释部分掩埋突变的所有子集中的稳定性，这意味着该距离足以容纳受主要分子内相互作用影响的残基，以保持蛋白质结构的稳定性。
For understanding the factors influencing protein stability, we have analyzed the relationship between changes in protein stability caused by partially buried mutations and changes in 48 physico-chemical, energetic and conformational properties of amino acid residues. Multiple regression equations were derived to predict the stability of protein mutants and the efficiency of the method has been verified with both back-check and jack-knife tests. We observed a good agreement between experimental and computed stabilities. Further, we have analyzed the effect of sequence window length from 1 to 12 residues on each side of the mutated residue to include the sequence information for predicting protein stability and we found that the preferred window length for obtaining the highest correlation is different for each secondary structure; the preferred window length for helical, strand and coil mutations are, respectively 0, 9 and 4 residues on both sides of the mutant residues. However, all the secondary structures have significant correlation for a window length of one residue on each side of the mutant position, implying the role of short-range interactions. Extraction of surrounding residue information for various distances (3 to 20 Angstrom) around the mutant position showed the highest correlation at 8 Angstrom, 6 Angstrom and 7 Angstrom, respectively, for mutations in helical, strand and coil segments. Overall, the information about the surrounding residues within the sphere of 7 to 8 Angstrom, may explain better the stability in all subsets of partially buried mutations implying that this distance is sufficient to accommodate the residues influenced by major intramolecular interactions for the stability of protein structures.