2.3. Co-evolution and conservation and analysis
The calculation of co-evolved residue pairs was based on Evcoupling webserver. Evcoupling can calculate co-evolution score for each residues in the corresponding protein family[20]. The co-evolution score reflect a network of interactions between residue pairs based on the evolutionary information in the family[21]. Conservation analysis was carried out by the ConSurf webserver (http://consurf.tau.ac.il/2016/) with HMMER E-value was set as 0.0001.