While BO runs initialized with the multi-alanine scanning strategy lags behind, no significant differences were observed among the other sequence-based strategies. Excluding the random search and multi-alanine scanning, all top-performing peptide sequences found at each DMT cycle fall within the 95 % confidence interval. For instance, initialized with the homolog scanning strategy, the best peptide sequences found show pIC50s close to the theoretical minima (8-mers: 1.30, 9-mers: -1.75, 10-mers: -1.58 and 11-mers: -0.25) after five DMT cycles: 1.70 ± 0.18, -1.26 ± 0.46, -1.25 ± 0.30 and 0.22 ± 0.30, for the 8-, 9-, 10-and 11-mers, respectively. Another observation is that the method is able to systematically find peptide sequences with better pIC50s compared to the previous DMT cycle. For instance, with 9-mers peptides, the initial DMT cycle improved the IC50 from roughly 100 nM to 1 nM for the best peptide sequence in the initial batch, corresponding to an improvement of 2 log units. Subsequent gains, however, decrease; two more DMT cycles (by the 3rd cycle) are necessary to achieve another tenfold improvement, and two more cycles to closely reach the theoretical minimum pIC50.