We also explore the usage of Diff-Shape in the structure-based drug design scenario by using the 3D conformation of a reference ligand for structure generation, followed by a docking calculation. Four protein pockets from the 2019 PDBBind dataset were selected for this evaluation (PDB IDs: 1z95, 4cra, 4m0y and 4w9c), and the X-ray binding conformations of ligand were used as references for Diff-Shape. We generated one thousand molecules per target and evaluated the binding affinity by using their GLIDE docking scores in the protein pockets as surrogates. As shown in Figure , docking scores of Diff-Shape-0.3 and Diff-Shape-0.4 generation sets, in general, outperforms all other methods. This highlights that compounds generated from the reference shape guided model might mimic the binding mode of reference compound and therefore has better docking score. The distributions of shape similarity of glide docking poses and 2D graph similarity to the reference ligands are shown in Figure .