The results show clear disparities between the different molecular representations on BO's performance (Fig. ). Only fine-tuned using the regular fine-tuning method after each DMT cycle with data from previous DMT cycles, pLMs such as ESM-1b and ProtT5 markedly outperform BO runs using the MAP4 fingerprint, reaching the theoretical minimum pIC50 in only 2 DMT cycles (Fig. , and S8, S9, S10 and S11). When not fine-tuned, pLMs perform poorly compared to the MAP4 fingerprint (Fig. and S7. Surprisingly, ESM-2 does not exhibit improved performance when fine-tuned. Meanwhile, BO runs using amino acid descriptors show erratic behavior (Fig. and) and the best molecular fingerprints tailored for small molecules (Morgan and MHFP) plateau after 1 DMT cycle (Fig. and). This stands in stark contrast to the MAP4 fingerprint which show consistent improvement over successive DMT cycles.