Fig. 5: Activity cliffs analysis.

Evaluate the bioactivity binding mode and the atom importance captured by our model on a (a) 5-phenyl-4-phenyldiazenyl-1,2-dihydropyrazol-3-one series and a (b) N-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine series. The binding modes of compound a1 and compound b1 in the active sites of GSK3β, with Protein Data Bank (PDB) ID: 3L1S, are predicted by AutoDock Vina⁵⁰ and visualized by PyMOL⁵¹. The key hydrogen bonds between compounds and the active sites are highlighted by yellow dash lines, while the green dash line refers to the intra-molecular halogen bond. The color intensity on each atom indicates its respective contribution to the prediction of our method, computed from a GNNExplainer⁴⁹.