title: HADDOCK: a protein-protein docking approach based on biochemical or biophysical information.
abstract: The structure determination of protein-protein complexes is a rather tedious and lengthy process, by both NMR and X-ray crystallography. Several methods based on docking to study protein complexes have also been well developed over the past few years. Most of these approaches are not driven by experimental data but are based on a combination of energetics and shape complementarity. Here, we present an approach called HADDOCK (High Ambiguity Driven protein-protein Docking) that makes use of biochemical and/or biophysical interaction data such as chemical shift perturbation data resulting from NMR titration experiments or mutagenesis data. This information is introduced as Ambiguous Interaction Restraints (AIRs) to drive the docking process. An AIR is defined as an ambiguous distance between all residues shown to be involved in the interaction. The accuracy of our approach is demonstrated with three molecular complexes. For two of these complexes, for which both the complex and the free protein structures have been solved, NMR titration data were available. Mutagenesis data were used in the last example. In all cases, the best structures generated by HADDOCK, that is, the structures with the lowest intermolecular energies, were the closest to the published structure of the respective complexes (within 2.0 A backbone RMSD).
authors.affiliation: Department of NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Utrecht University, 3584CH, Utrecht, The Netherlands.
authors.forename: Cyril
authors.initials: C
authors.lastname: Dominguez
authors.forename: Rolf
authors.initials: R
authors.lastname: Boelens
authors.forename: Alexandre M J J
authors.initials: AM
authors.lastname: Bonvin
mesh_terms: D001426:Bacterial Proteins; D015704:CD4 Antigens / Q000737:chemistry; D029968:Escherichia coli Proteins; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000737:chemistry; D020836:Protein Structure, Quaternary; D011506:Proteins / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D015704:CD4 Antigens; D029968:Escherichia coli Proteins; D015699:HIV Envelope Protein gp120; D011506:Proteins; C032242:crr protein, E coli; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; C030182:phosphocarrier protein HPr