title: Application of the ATTRACT Coarse-Grained Docking and Atomistic Refinement for Predicting Peptide-Protein Interactions.
abstract: 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.
authors.affiliation: Physics Department (T38), Center for Integrated Protein Science Munich (CIPSM), Technical University of Munich, James-Franck-Str. 1, 85748, Garching, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Schindler
authors.affiliation: Physics Department (T38), Center for Integrated Protein Science Munich (CIPSM), Technical University of Munich, James-Franck-Str. 1, 85748, Garching, Germany. martin.zacharias@mytum.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Zacharias
mesh_terms: D001665:Binding Sites; D030562:Databases, Protein; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry / Q000378:metabolism; D012984:Software; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism; D064878:Web Browser
chemical_list: D010446:Peptide Fragments; D011506:Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Coarse-graining; Docking minimization; Ensemble docking; Flexible interface refinement; Fully blind peptide-protein docking; Molecular dynamics refinement; Peptide flexibility; Peptide-protein complex formation; Proteome-wide modeling