title: Solvated protein-DNA docking using HADDOCK.
abstract: Interfacial water molecules play an important role in many aspects of protein-DNA specificity and recognition. Yet they have been mostly neglected in the computational modeling of these complexes. We present here a solvated docking protocol that allows explicit inclusion of water molecules in the docking of protein-DNA complexes and demonstrate its feasibility on a benchmark of 30 high-resolution protein-DNA complexes containing crystallographically-determined water molecules at their interfaces. Our protocol is capable of reproducing the solvation pattern at the interface and recovers hydrogen-bonded water-mediated contacts in many of the benchmark cases. Solvated docking leads to an overall improvement in the quality of the generated protein-DNA models for cases with limited conformational change of the partners upon complex formation. The applicability of this approach is demonstrated on real cases by docking a representative set of 6 complexes using unbound protein coordinates, model-built DNA and knowledge-based restraints. As HADDOCK supports the inclusion of a variety of NMR restraints, solvated docking is also applicable for NMR-based structure calculations of protein-DNA complexes.
authors.affiliation: Bijvoet Center for Biomolecular Research, Faculty of Science-Chemistry, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: van Dijk
authors.forename: Koen M
authors.initials: KM
authors.lastname: Visscher
authors.forename: Panagiotis L
authors.initials: PL
authors.lastname: Kastritis
authors.forename: Alexandre M J J
authors.initials: AM
authors.lastname: Bonvin
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012997:Solvents / Q000737:chemistry / Q000378:metabolism; D014867:Water / Q000737:chemistry / Q000378:metabolism*
chemical_list: D046911:Macromolecular Substances; D011506:Proteins; D012997:Solvents; D014867:Water; D004247:DNA