• Scaffold diversity. Designing molecules with novel scaffolds bears relevance in lead identification , and can be used as a proxy to evaluate CLMs . Here, to have a better evaluation of what constitutes a novel scaffold, the novel designs were grouped in clusters based on their scaffold similarity. This was achieved via hierarchical clustering, to group designs with similar Bemis-Murcko scaffolds (as computed via the Tanimoto similarity on the corresponding extended connectivity fingerprints higher than 60%). Only novel and unique scaffolds were considered. We then counted the number of obtained scaffold clusters, the higher, the better.