When filtering out designs with a fragment similarity (Tanimoto index on Morgan fingerprints ) greater than 50% of the respective fine-tuning molecules, the difference between multinomial sampling and beam searching was less pronounced (Fig. , Supplementary Figs. ). Multinomial sampling identified molecules with lower perplexity scores than the beam search in 72% of the cases involving the smallest fine-tuning sets (Supplementary Table ). The deterioration in performance for highly diverse molecules was less pronounced with the larger fine-tuning sets (Supplementary Table ).