Matching protein surface structural patches for high-resolution blind peptide docking

Abstract

Significance Modeling interactions between short peptides and their receptors is a challenging docking problem due to the peptide flexibility, resulting in a formidable sampling problem of peptide conformation in addition to its orientation. Alternatively, the peptide can be viewed as a piece that complements the receptor monomer structure. Here, we show that the peptide conformation can be determined based on the receptor backbone only and sampled using local structural motifs found in solved protein monomers and interfaces, independent of sequence similarity. This approach outperforms current peptide docking protocols and promotes new directions for peptide interface design.