Department of Life Sciences, Ben-Gurion University of the Negev, 84105, Be'er Sheva, Israel.
Cell Mol Life Sci. 2014 Feb;71(4):673-82. doi: 10.1007/s00018-013-1458-2. Epub 2013 Sep 1.
Computational approaches for detecting co-evolution in proteins allow for the identification of protein-protein interaction networks in different organisms and the assignment of function to under-explored proteins. The detection of co-variation of amino acids within or between proteins, moreover, allows for the discovery of residue-residue contacts and highlights functional residues that can affect the binding affinity, catalytic activity, or substrate specificity of a protein. To explore the functional impact of co-evolutionary changes in proteins, a combined experimental and computational approach must be recruited. Here, we review recent studies that apply computational and experimental tools to obtain novel insight into the structure, function, and evolution of proteins. Specifically, we describe the application of co-evolutionary analysis for predicting high-resolution three-dimensional structures of proteins. In addition, we describe computational approaches followed by experimental analysis for identifying specificity-determining residues in proteins. Finally, we discuss studies addressing the importance of such residues in terms of the functional divergence of proteins, allowing proteins to evolve new functions while avoiding crosstalk with existing cellular pathways or forming reproductive barriers and hence promoting speciation.
计算方法可用于检测蛋白质中的共进化，从而鉴定不同生物体中的蛋白质-蛋白质相互作用网络，并为研究不足的蛋白质赋予功能。此外，检测蛋白质内部或之间氨基酸的共变，还可以发现残基-残基接触，并突出功能残基，这些残基可能影响蛋白质的结合亲和力、催化活性或底物特异性。为了探索蛋白质共进化变化的功能影响，必须采用综合的实验和计算方法。在这里，我们综述了最近应用计算和实验工具的研究，以获得对蛋白质结构、功能和进化的新认识。具体来说，我们描述了共进化分析在预测蛋白质高分辨率三维结构中的应用。此外，我们还描述了通过计算方法和实验分析来确定蛋白质中决定特异性的残基的方法。最后，我们讨论了这些残基在蛋白质功能分化方面的重要性，这使得蛋白质能够进化出新的功能，同时避免与现有细胞途径发生交叉对话或形成生殖障碍，从而促进物种形成。
