Cavity volume spreads repeat the trend seen with electric field spreads with RNA/DNA and histone MTases having standard deviations of 231.0 Å 3 and 162.9 Å 3 , respectively. We believe the increased variation in volume for RNA/DNA targeting enzymes reflects the geometric diversity seen in nucleic acid substrates. Target atoms in nucleic acid substrates have diverse locations within their respective residues and have both sp 2 and sp 3 hybridization whereas all histone targets have the same sp 3 hybridization. The transparent amino acids are colored red and blue when they contribute > 5.0 MV/cm and < -5.0 MV/cm to the electric field, respectively. Inlay (c) shows a structure that has no metal ions present. SAM is rendered as grey spheres in both (b) and (c).