Peptide arrays facilitate the exploration of protein-protein interactions, allowing for analysis at the amino acid level. This study introduces a “deep screening” technique to represent entire proteomes with peptides, thereby revealing novel interactions that are not detectable with protein-only methods. We developed a method to construct a peptide library based on genomic peptide similarity, prioritizing peptides with the highest occurrence in the proteome. Using the monoclonal anti-CD20 antibody rituximab, we demonstrate the process of peptide library design, incubation, and photometric data acquisition. The method also includes hit validation through dissociation constant measurements and substitutional analysis to identify key amino acids for binding. This innovative approach enhances the identification of peptide interactions, offering significant potential for diagnostic and therapeutic developments.