Computational design of peptide ligands

Peptides possess several attractive features when compared to small molecule and protein therapeutics, such as high structural compatibility with target proteins, the ability to disrupt protein–protein interfaces, and small size. Efficient design of high-affinity peptide ligands via rational methods has been a major obstacle to the development of this potential drug class. However, structural insights into the architecture of protein–peptide interfaces have recently culminated in several computational approaches for the rational design of peptides that target proteins. These methods provide a valuable alternative to experimental high-resolution structures of target protein–peptide complexes, bringing closer the dream of in silico designed peptides for therapeutic applications.