Å 3 ), further suggesting that the enzymes do not directly adjust their volumes to accommodate different heteroatoms. Furthermore, we investigated how interior electric field and cavity adapt to substrates with different hybridization state of nitrogen atoms. We emphasized the N-targeting MTases for RNA/DNA and histones because they are the two largest substrate types in the dataset with 50 and 21 enzymes catalyzing for these reactants, respectively. Nucleic acids are more diverse, containing nitrogen in both sp 2 and sp 3 hybridization states (Figure ). Histone MTases target nitrogen on lysine residues in sp 3 hybridization only. Notably, the amine group with sp 3 N can also have varying protonation states depending on local chemical environment. Wide distribution of electric field strengths along the S-C bonds mirror this diversity, with RNA/DNA and histone MTases having standard deviations of 121.4 MV/cm and 55.3 MV/cm, respectively (Figure ).