Main methods and tools for peptide development based on protein-protein interactions (PPIs)

Protein-protein interactions (PPIs) regulate essential physiological and pathological processes. Due to their large and shallow binding surfaces, PPIs are often considered challenging drug targets for small molecules. Peptides offer a viable alternative, as they can bind these targets, acting as regulators or mimicking interaction partners. This review focuses on competitive peptides, a class of orthosteric modulators that disrupt PPI formation. We provide a concise yet comprehensive overview of recent advancements in in-silico peptide design, highlighting computational strategies that have improved the efficiency and accuracy of PPI-targeting peptides. Additionally, we examine cutting-edge experimental methods for evaluating PPI-based peptides. By exploring the interplay between computational design and experimental validation, this review presents a structured framework for developing effective peptide therapeutics targeting PPIs in various diseases.