Gromiha M M, Oobatake M, Kono H, Uedaira H, Sarai A
RIKEN Tsukuba Institute, The Institute of Physical and Chemical Research, Ibaraki, Japan.
J Biomol Struct Dyn. 2000 Oct;18(2):281-95. doi: 10.1080/07391102.2000.10506666.
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 20A) around the mutant position showed the highest correlation at 8A, 6A and 7A, respectively, for mutations in helical, strand and coil segments. Overall, the information about the surrounding residues within the sphere of 7 to 8A, 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.
为了理解影响蛋白质稳定性的因素，我们分析了由部分埋藏突变引起的蛋白质稳定性变化与氨基酸残基的48种物理化学、能量和构象性质变化之间的关系。推导了多元回归方程来预测蛋白质突变体的稳定性，并且该方法的有效性已通过回查和留一法检验得到验证。我们观察到实验稳定性和计算稳定性之间有良好的一致性。此外，我们分析了突变残基两侧1至12个残基的序列窗口长度对预测蛋白质稳定性的序列信息的影响，发现获得最高相关性的首选窗口长度因每种二级结构而异；对于螺旋、链和卷曲突变，突变残基两侧的首选窗口长度分别为0、9和4个残基。然而，对于突变位置两侧各一个残基的窗口长度，所有二级结构都有显著相关性，这意味着短程相互作用的作用。提取突变位置周围不同距离（3至20埃）的周围残基信息显示，对于螺旋、链和卷曲片段中的突变，分别在8埃、6埃和7埃处具有最高相关性。总体而言，7至8埃范围内周围残基的信息可以更好地解释部分埋藏突变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维持蛋白质结构的稳定性。
