Peptides and peptidomimetics have gained increasing traction in recent years for drug design and biochemical applications . Despite progress in peptide synthesis using Solid-Phase Peptide Synthesis (SPPS) , the combinatorial explosion of peptide sequence candidates renders exhaustive exploration impossible. For instance, if a peptide with a length of only 10 amino acids is to be designed, the number of possibilities is 20 10 ≈ 1.02 × 10 13 , considering only the use of standard amino acids. Furthermore, the amount of experimental data available is usually relatively low, and the cost of experiments to acquire more data is high. This presents a challenge for the development of bioactive peptides. BO is well-suited for this task, where the goal is to selectively explore the sequence space and test only the most promising candidates. , 6vr1 (9-mers, HMTEVVRRC) , 6amt (10-mers, MMWDRGLGMM), 5d9s (11-mers, FVLELEPEWTV) , and 5fa4 (11-mers, YLSPIASPLLD) . The MHC receptor and co-crystallized peptides are represented in cartoon. The MHC receptor is colored white, while bound peptides are colored using the following color code: greencyan (1duy), skyblue (6vr1), orange (6amt), deep-salmon (5d9s), and red (5fa4). Pocket A with the anchoring pockets B and F are indicated by dotted circles. Pocket A binds the N-terminal part of the peptide, while the C-terminal binds into the F pocket. Peptides N-and C-termini are represented by a sphere. (B) Sequence motifs binding to the MHC class I A*0201 for each peptide length, from 8-mers to 11-mers, are represented as logo plots using LogoMaker . SMM PMBEC (Stabilized Matrix Method, Peptide:MHC Binding Energy Covariance) scoring matrices were used as input to LogoMaker. The y-axis indicates the inhibition contribution expressed in negative pIC50 value for each amino acid at each position. A negative pIC50 value contributes positively to the inhibition. Amino acids that contribute negatively (positive pIC50 values) to the inhibition are not represented. Chemistry settings were used: polar amino acids (G, S, T, Y, C, Q, N) are green, basic (K, R, H) blue, acidic (D, E) red, and hydrophobic (A, V, L, I, P, W, F, M) amino acids are black.