The functional importance of co-evolving residues in proteins

Inga Sandler, Nitzan Zigdon, Efrat Levy, Amir Aharoni

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations


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.

Original languageEnglish
Pages (from-to)673-682
Number of pages10
JournalCellular and Molecular Life Sciences
Issue number4
StatePublished - 1 Feb 2014


  • Ancestral proteins
  • Co-evolution
  • Protein-protein interactions
  • Speciation
  • Specificity-determining residues

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology


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