. The available structures followed a simple protonation scheme considering neutral pH: (i) all carboxylic acid and phosphate groups were deprotonated, and (ii) all aliphatic amine, guanidine, and amidine groups were protonated. Interestingly, all histidine residues exhibit an unusual negatively charged protonation state, as no hydrogen atoms are attached to the side chain nitrogen atoms. This unusual protonation state of histidines needs correction, as the accurate assignment of both protein and ligand protonation/tautomeric states is crucial for predicting binding modes and affinities. This is just an example to justify the need to carefully treat the structures .