Identification of residues involved in water versus glycerol selectivity in aquaporins by differential residue pair co-evolution

► Aquaporins can be separated phylogenetically in water and glycerol transporters. ► SCA reveals residues important for substrate recognition in aquaporins. ► Most of these residues are close to the lumen of the pore. ► Most of these residues are in the extracellular half of the protein.