Fig. 4

“Mesh globes” in the figure indicate the frequency with which that toxicophores appears in drugs associated with TdP risk. Each globe can be thought of as a possible toxicophore in a “3D Query panel” (MOE software). Features #1 and #2 represents two planar Pi rings. Feature #3 (green) illustrates a hydrophobic centroid (Hyd) and features #4 elucidates a Polar-Charged-Hydrophobic scheme assigns the label Aro (aromatic center) to a hydrophobic area. Feature #5 (F5) shows a cationic atom and a H-bond donor. Identification of these five features is not dependent on any of normal QSAR modeling. Therefore, the fact that these show up with some frequency in a subset of the data that includes only TdP positive compounds may or may not indicate that they are necessary participants causing TdP