Co-evolutionary landscape at the interface and non-interface regions of protein-protein interaction complexes

Proteins involved in interactions throughout the course of evolution tend to co-evolve and compensatory changes may occur interacting proteins maintain or refine such interactions. However, certain residue pair alterations prove be detrimental for functional Hence, determining co-evolutionary pairings that could structurally functionally relevant maintaining conservation an inter-protein interaction is important. Inter-protein co-evolution analysis several complexes utilizing multiple existing methodologies suggested can spatially proximal distant regions Subsequently, Co-Var (Correlated Variation) method based on mutual information Bhattacharyya coefficient was developed, validated, found perform relatively better than CAPS EV-complex. Interestingly, while applying measure EV-complex program a set protein–protein complexes, were obtained interface non-interface protein complexes. The approach involves high degree include connections between particular co-evolved positions one with binding partner. Detailed analyses cancer metastasis most forming mainly occurred within domains constituent substitution mutations also common among these positions. physiological relevance predictions predict residues crucial preserving Finally, web server (http://www.hpppi.iicb.res.in/ishi/covar/index.html) implements this methodology identifies intra