Indeed, using just these two ErG bits as filters and selecting non-null values for them in the ErG description of ligands, we ended up with 92% of the entire dataset. The remaining ligands with null values with any of the two selected ErG bits are not involved with CRBN or VHL but only with "Other" class of E3 ligases. In the confusion matrix, we report in Figure in supplementary materials, it can be appreciated for the accuracy of the six classes of E3 ligases used. Diving deeper in the ErG bits space, we tried to evaluate statistical relevance of what has been found as top ten relevant features and how their differences are distributed along the six E3 ligase classes. Indeed, not all the distributions found around these ErG bits are statistically significant but there are some which are pretty informative (Figure ). While Hf_D_d2 is clearly a footprint for VHL only (probably due to the already mentioned hydroxy proline residue), and Hf_Ac_d2 is a marker for CRBN, another selective CRBN pharmacophoric point is Ac_Ac_d4 which is related to the distance between the two carbonyl oxygens in the succinimide ring and the mono or di carbonyl oxygens positioned in the attached phthalimide ring. ErG bit D_Ac_d5 seems to be another marker for VHL (highest count) especially against the "Other" group of Ligases which do not show any count on this feature distance. Hf_D_d4 and D_Ac_d3 seem to mark CIAP1, IAP and XIAP ligands as they are contained in hydrophobic aliphatic amino acids and amino acids, respectively. Both are well represented in these three groups. CIAP1 and XIAP only have the largest count of Ar_Ac_d9, while Hf_Ac_d9 has the least significant contribution according to its distribution in the six groups (Figure ).