Tunnels conservation
In the last years, attention to the presence of tunnels has increased due to their importance to explain structure-function relationships in proteins45. Tunnels allow the transit of ligands from the outside (and vice versa) of the protein to inner cavities containing active and binding sites. Overall, their structure and physicochemical properties define binding constants for ligands. Along with protein dynamism, tunnels also define active and inactive conformations just allowing the opening or closing of cavity access45–47. Using the program MOLE, we identified a common tunnel linking Lys 199 and Arg 222 with the surface in HSA and their structurally equivalent residues in BSA and RabSA. At the bottom of the tunnel, we also found the conserved residue Arg 218 which is spatially close to Lys 199 and Arg 222 (Figure 4). Interestingly, at the entrance of the tunnel, we found a mostly conserved positively charged residue (His, Arg, or Lys). This residue, an His in HSA (His 440), along with Arg 218 are evolving under a positive selection process involved in functional adaptations. Our hypothesis is that this tunnel common to HSA, BSA, and RSA allows the transit of biologically important ligands up to the cavity where Lys 199 and Arg 222 are found.