Innovative strategies for modeling peptide–protein interactions and rational peptide drug design

This review highlights cutting-edge techniques for modeling peptide–protein interactions and advancing computer-aided peptide–drug design. We examine significant progress in generating peptide poses through docking and artificial intelligence (AI), assessing peptide flexibility via enhanced molecular dynamics simulations, and analyzing binding interactions through free energy calculations. Additionally, we discuss how these insights can inform the rational design of therapeutic peptides by utilizing free energy metrics and strategic modifications to enhance their binding affinity and therapeutic potential. Looking forward, further integrating AI will be crucial for optimizing peptide design and enhancing drug development efforts.