For example, Imatinib has three reported on-targets (assigned in PKIDB) and two offtargets (based on activity data in the Karaman-Davis dataset); KiSSim's performance is The tree is based on a clustering of the kinase distance matrix using as metric the Euclidian distance and as linkage Ward's criterion. The clusters are converted to the Newick format and visualized using FigTree. See notebook for more details. evaluated by checking for these five Imatinib targets in KiSSim's most similar kinases to the on-targets (1) ABL1, (2) KIT, and (3) FMS, producing three ROC curves (Figure , first row, second plot). Details are described in the KiSSim evaluation using profiling data section. In total, we analyzed KiSSim's performance across 48 kinase-ligand pairs involving 21 ligands; the AUCs range from 0.49 to 1.0 with a mean of 0.75 ± 0.12. In the following, The top 20 KiSSim ranks for EGFR are dominated by TK kinases but include the STE kinases LOK and SLK on ranks 11 and 20 out of the 50 shared kinases, respectively; the GAK kinase is not detected by KiSSim, being found on rank 44 only (AUC = 0.641). The EGFR-GAK fingerprint pair shows many differences in their physicochemical bits, which stem from their relatively high pocket sequence dissimilarity (Figure ). The fingerprint differences for the EGFR-GAK pair are visualized in 3D in Figure for selected fingerprint features with high differences such as the HBA, aliphatic, and the hinge region features.