As a first step towards that goal, we used the Major Histocompatibility Complex (MHC) class I receptor system to validate and assess BO performance in diverse scenarios. Briefly, MHC class I has the role of capturing peptide antigens and displaying them on cell surfaces, enabling recognition by T cells . MHC class I binds short peptides, typically between 8 and 11 residues. The N-and C-terminal ends of the peptides are locked at specific locations in the binding groove , with pockets B and F serving as the primary anchoring points (Fig. ). However, longer peptides can also bind to MHC class I by adopting bulging conformations while maintaining the conserved hydrogen bonding network at the peptide's N-and C-terminus . Its crucial role in the adaptive immune system makes it the most intensively studied protein-peptide complex. Given the extensive binding data available for this system, a digital twin can be constructed, allowing for querying reliable log 10 (IC50) (pIC50) values for any peptide sequence with a length between 8 and 11 residues (8-to 11-mers) with no additional experiments required (Fig. ). This opens the door to the construction of a virtual closed-loop DMT system, enabling the systematic evaluations of BO for peptide optimization tasks.