Application of the ATTRACT coarse-grained docking and atomistic refinement for predicting peptide-protein interactions

Peptide-protein interactions are abundant in the cell and form an important part of the interactome. Large-scale modeling of peptide-protein complexes requires a fully blind approach; i.e., simultaneously predicting the peptide-binding site and the peptide conformation to high accuracy. Here, we present one of the first fully blind peptide-protein docking protocols, pepATTRACT. It combines a coarse-grained ensemble docking search of the entire protein surface with two stages of atomistic flexible refinement. pepATTRACT yields high-quality predictions for 70 % of the cases when tested on a large benchmark of peptide-protein complexes. This performance in fully blind mode is similar to state-of-the-art local docking approaches that use information on the location of the binding site. Limiting the search to the peptide-binding region, the resulting pepATTRACT-local approach further improves the performance. Docking scripts for pepATTRACT and pepATTRACT-local can be generated via a web interface at www.attract. ph.tum.de/peptide.html. Here, we explain how to set up a docking run with the pepATTRACT web interface and demonstrate its usage by an application on binding of disordered regions from tumor suppressor p53 to a partner protein.