However, it cannot be ruled out that the interatomic distances may be predicted to be short by chance when considering the results of a single docking analysis. Therefore, to exclude these coincidental predictions, we conducted further detailed docking analyses (Figure ). Specifically, we calculated the average and standard deviation of the interatomic distances C22-C18', N-C18', and Fe-C18' for all 22 potential docking conformers derived from the docking analysis of 3 and CttpC in the known rational active site (Figure ). The average interatomic distances for 3 in the presence of CttpC were C22-C18': 13.4 Å, N-C18': 12.6 Å, and Fe-C18': 10.6 Å, with low standard deviations of C22-C18': 3.41, N-C18': 2.15, and Fe-C18': 1.38. These results indicate that the macrocyclization of 3 catalyzed by CttpC is crucial for the proper positioning of the two tryptophan moieties and hemoglobin, as evidenced by computational results and docking analysis.