Non-sequential alignment of binding sites for fast peptide screening

Motivation Peptides are molecules involved in many essential biological activities by interacting with proteins in the body. They can also be used as therapeutic molecules, particularly to disrupt protein-protein interactions involved in disease. However, it is difficult to identify potential therapeutic peptides if the structure of the protein-protein complex to be inhibited has not been solved. Results The PepIT program was developed to propose peptides that can interact with a given protein. PepIT is based on a non-sequential alignment algorithm to identify peptide binding sites that share geometrical and physicochemical properties with a surface region of the target protein. PepIT compares the entire surface of the target protein with the peptide binding sites of the Propedia dataset, which contains more than 19,000 high-resolution protein-peptide structures. Once a peptide binding site similar to a portion of the protein surface is found, the peptide bound to the binding site is repositioned on the corresponding portion of the protein surface. Availability and implementation The PepIT source code is freely available at https://github.com/DSIMB/pepit Supplementary information Supplementary data are available online.