In addition to NP-likeness, we evaluated the novel designs in terms of several structural properties important for natural products , namely: the number of sp 3 -hybridized carbon atoms, aliphatic rings, spiro atoms and heavy atoms, as well as the molecular weight and the size of the largest fused ring system. These properties provide additional evidence on the molecular characteristics of the designs, and their structural complexity in comparison with the training natural products. Here, S4 achieved the lowest KS distance to the training and test sets across the board, indicating that its designs match the training natural products best. These results confirm the ability of S4 to learn complex molecular properties for de novo design.