Computational Tools and Strategies to Develop Peptide-Based Inhibitors of Protein-Protein Interactions

Protein-protein interactions play crucial and subtle roles in many biological processes and modifications of their fine mechanisms generally result in severe diseases. Peptide derivatives are very promising therapeutic agents for modulating protein-protein associations with sizes and specificities between those of small compounds and antibodies. For the same reasons, rational design of peptide-based inhibitors naturally borrows and combines computational methods from both protein-ligand and protein-protein research fields. In this chapter, we aim to provide an overview of computational tools and approaches used for identifying and optimizing peptides that target protein-protein interfaces with high affinity and specificity. We hope that this review will help to implement appropriate in silico strategies for peptide-based drug design that builds on available information for the systems of interest.