title: Solvated protein-protein docking using Kyte-Doolittle-based water preferences.
abstract: HADDOCK is one of the few docking programs that can explicitly account for water molecules in the docking process. Its solvated docking protocol starts from hydrated molecules and a fraction of the resulting interfacial waters is subsequently removed in a biased Monte Carlo procedure based on water-mediated contact probabilities. The latter were derived from an analysis of water contact frequencies from high-resolution crystal structures. Here, we introduce a simple water-mediated amino acid-amino acid contact probability scale derived from the Kyte-Doolittle hydrophobicity scale and assess its performance on the largest high-resolution dataset developed to date for solvated docking. Both scales yield high-quality docking results. The novel and simple hydrophobicity scale, which should reflect better the physicochemical principles underlying contact propensities, leads to a performance improvement of around 10% in ranking, cluster quality and water recovery at the interface compared with the statistics-based original solvated docking protocol.
authors.affiliation: Bijvoet Center for Biomolecular Research, Faculty of Science, Department of Chemistry, Utrecht University, Padualaan 8, 3584CH, Utrecht, The Netherlands.
authors.forename: Panagiotis L
authors.initials: PL
authors.lastname: Kastritis
authors.forename: Koen M
authors.initials: KM
authors.lastname: Visscher
authors.forename: Aalt D J
authors.initials: AD
authors.lastname: van Dijk
authors.forename: Alexandre M J J
authors.initials: AM
authors.lastname: Bonvin
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000936:Antigen-Antibody Complex / Q000737:chemistry; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D046912:Multiprotein Complexes / Q000737:chemistry*; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D015203:Reproducibility of Results; D012984:Software; D014867:Water / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D000936:Antigen-Antibody Complex; D004791:Enzyme Inhibitors; D046912:Multiprotein Complexes; D014867:Water