Noivirt Orly, Eisenstein Miriam, Horovitz Amnon
Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Protein Eng Des Sel. 2005 May;18(5):247-53. doi: 10.1093/protein/gzi029. Epub 2005 May 23.
Direct or indirect inter-residue interactions in proteins are often reflected by mutations at one site that compensate for mutations at another site. Various bioinformatic methods have been developed for detecting such correlated mutations in order to obtain information about intra- and inter-protein interactions. Here, we show by carrying out a correlated mutation analysis for non-interacting proteins that the signal due to inter-residue interactions is of similar magnitude to the 'noise' that arises from other evolutionary processes related to common ancestry. A new method for detecting correlated mutations is presented that reduces this evolutionary noise by taking into account evolutionary distances in the protein family. It is shown that this method yields better signal-to-noise ratios and, therefore, can much better resolve, for example, correlated mutations that reflect true inter-residue interactions.
蛋白质中直接或间接的残基间相互作用通常通过一个位点的突变来反映，该突变可补偿另一个位点的突变。为了获得有关蛋白质内和蛋白质间相互作用的信息，已经开发了各种生物信息学方法来检测这种相关突变。在这里，我们通过对非相互作用蛋白质进行相关突变分析表明，由于残基间相互作用产生的信号与源于与共同祖先相关的其他进化过程的“噪声”大小相似。提出了一种检测相关突变的新方法，该方法通过考虑蛋白质家族中的进化距离来减少这种进化噪声。结果表明，该方法具有更好的信噪比，因此，例如，可以更好地解析反映真实残基间相互作用的相关突变。
