title: DrugScorePPI knowledge-based potentials used as scoring and objective function in protein-protein docking.
abstract: The distance-dependent knowledge-based DrugScore(PPI) potentials, previously developed for in silico alanine scanning and hot spot prediction on given structures of protein-protein complexes, are evaluated as a scoring and objective function for the structure prediction of protein-protein complexes. When applied for ranking "unbound perturbation" ("unbound docking") decoys generated by Baker and coworkers a 4-fold (1.5-fold) enrichment of acceptable docking solutions in the top ranks compared to a random selection is found. When applied as an objective function in FRODOCK for bound protein-protein docking on 97 complexes of the ZDOCK benchmark 3.0, DrugScore(PPI)/FRODOCK finds up to 10% (15%) more high accuracy solutions in the top 1 (top 10) predictions than the original FRODOCK implementation. When used as an objective function for global unbound protein-protein docking, fair docking success rates are obtained, which improve by ∼ 2-fold to 18% (58%) for an at least acceptable solution in the top 10 (top 100) predictions when performing knowledge-driven unbound docking. This suggests that DrugScore(PPI) balances well several different types of interactions important for protein-protein recognition. The results are discussed in view of the influence of crystal packing and the type of protein-protein complex docked. Finally, a simple criterion is provided with which to estimate a priori if unbound docking with DrugScore(PPI)/FRODOCK will be successful.
authors.affiliation: Institute for Pharmaceutical and Medicinal Chemistry, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Krüger
authors.affiliation: Rocasolano Physical Chemistry Institute, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Ignacio Garzón
authors.affiliation: Rocasolano Physical Chemistry Institute, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Chacón
authors.affiliation: Institute for Pharmaceutical and Medicinal Chemistry, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Gohlke
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D051188:Knowledge Bases; D062105:Molecular Docking Simulation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D020836:Protein Structure, Quaternary; D011506:Proteins / Q000737:chemistry*; D012984:Software; D018709:Statistics, Nonparametric; D013816:Thermodynamics
chemical_list: D011506:Proteins