Interacting biomolecules tend to coevolve, and compensatory or coordinated residue changes may occur to preserve functional interactions. Predicting coevolutionary pairings could be important for determining structurally and functionally important residues in complexes or interfaces. Correlated variation (Co-Var) aims to determine both intramolecular and intermolecular coevolving residues in proteins, protein-protein, protein-DNA, or protein-RNA complexes. It utilizes two statistical parameters namely mutual information and Bhattacharyya coefficient. In this article, we have described how to utilize the Co-Var method to identify coevolutionary parings within and/or across biomolecules.
Keywords: Coevolving residues; Intermolecular coevolution; Mutual information; Sequence homology; Sequence–structure relationships.
© 2026. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.