title: Information-Driven, Ensemble Flexible Peptide Docking Using HADDOCK.
abstract: Modeling protein-peptide interactions remains a significant challenge for docking programs due to the inherent highly flexible nature of peptides, which often adopt different conformations whether in their free or bound forms. We present here a protocol consisting of a hybrid approach, combining the most frequently found peptide conformations in complexes with representative conformations taken from molecular dynamics simulations of the free peptide. This approach intends to broaden the range of conformations sampled during docking. The resulting ensemble of conformations is used as a starting point for information-driven flexible docking with HADDOCK. We demonstrate the performance of this protocol on six cases of increasing difficulty, taken from a protein-peptide benchmark set. In each case, we use knowledge of the binding site on the receptor to drive the docking process. In the majority of cases where MD conformations are added to the starting ensemble for docking, we observe an improvement in the quality of the resulting models.
authors.affiliation: Computational Structural Biology Group, Bijvoet Center for Biomolecular Research, Faculty of Science-Chemistry, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
authors.forename: Cunliang
authors.initials: C
authors.lastname: Geng
authors.affiliation: Computational Structural Biology Group, Bijvoet Center for Biomolecular Research, Faculty of Science-Chemistry, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
authors.forename: Siddarth
authors.initials: S
authors.lastname: Narasimhan
authors.affiliation: Computational Structural Biology Group, Bijvoet Center for Biomolecular Research, Faculty of Science-Chemistry, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.|Department of Structural Biology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA, 94305, USA.
authors.forename: João P G L M
authors.initials: JP
authors.lastname: Rodrigues
authors.affiliation: Computational Structural Biology Group, Bijvoet Center for Biomolecular Research, Faculty of Science-Chemistry, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands. a.m.j.j.bonvin@uu.nl.
authors.forename: Alexandre M J J
authors.initials: AM
authors.lastname: Bonvin
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*; D012984:Software; D064878:Web Browser
chemical_list: D010446:Peptide Fragments; D011506:Proteins
keywords: Ensemble docking; Flexibility; HADDOCK; Information-driven docking; Molecular dynamics simulations; Protein-peptide docking