title: AnchorDock for Blind Flexible Docking of Peptides to Proteins.
abstract: Due to increasing interest in peptides as signaling modulators and drug candidates, several methods for peptide docking to their target proteins are under active development. The "blind" docking problem, where the peptide-binding site on the protein surface is unknown, presents one of the current challenges in the field. AnchorDock protocol was developed by Ben-Shimon and Niv to address this challenge.This protocol narrows the docking search to the most relevant parts of the conformational space. This is achieved by pre-folding the free peptide and by computationally detecting anchoring spots on the surface of the unbound protein. Multiple flexible simulated annealing molecular dynamics (SAMD) simulations are subsequently carried out, starting from pre-folded peptide conformations, constrained to the various precomputed anchoring spots.Here, AnchorDock is demonstrated using two known protein-peptide complexes. A PDZ-peptide complex provides a relatively easy case due to the relatively small size of the protein, and a typical peptide conformation and binding region; a more challenging example is a complex between USP7N-termand a p53-derived peptide, where the protein is larger, and the peptide conformation and a binding site are generally assumed to be unknown. AnchorDock returned native-like solutions ranked first and third for the PDZ and USP7 complexes, respectively. We describe the procedure step by step and discuss possible modifications where applicable.
authors.affiliation: The Institute of Biochemistry, Food Science and Nutrition, The Robert H Smith Faculty of Agriculture, Food and Environment, and the Fritz Haber Center for Molecular Dynamics, The Hebrew University, 12, Rehovot, 76100, Jerusalem, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Slutzki
authors.affiliation: The Institute of Biochemistry, Food Science and Nutrition, The Robert H Smith Faculty of Agriculture, Food and Environment, and the Fritz Haber Center for Molecular Dynamics, The Hebrew University, 12, Rehovot, 76100, Jerusalem, Israel.
authors.forename: Avraham
authors.initials: A
authors.lastname: Ben-Shimon
authors.affiliation: The Institute of Biochemistry, Food Science and Nutrition, The Robert H Smith Faculty of Agriculture, Food and Environment, and the Fritz Haber Center for Molecular Dynamics, The Hebrew University, 12, Rehovot, 76100, Jerusalem, Israel. masha.niv@mail.huji.ac.il.
authors.forename: Masha Y
authors.initials: MY
authors.lastname: Niv
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; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism; D000076084:Ubiquitin-Specific Peptidase 7 / Q000737:chemistry / Q000378:metabolism; D064878:Web Browser
chemical_list: D010446:Peptide Fragments; D011506:Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C464569:USP7 protein, human; D000076084:Ubiquitin-Specific Peptidase 7
keywords: Anchors; Binding site prediction; Peptide docking; Peptide folding; Simulated annealing molecular dynamics; Surface mapping