The average RMSD values (of the top ten scoring poses per each enzyme isoform) of the validated docking protocol ranged from 1.82 to 1.9 for carbonic anhydrases I, II, and IX, while carbonic anhydrase XII had an average RMSD value of 3.36. The major reason behind the elevated average RMSD value for carbonic anhydrase XII is the removal of a water molecule, during receptor preparation, located in a shallow groove that is directly adjacent to Acetazolamide in its co-crystallized state; thus the docked Acetazolamide deviates because of the missing steric support of this removed water molecule.