Solvated protein–DNA docking using HADDOCK
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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.
KeywordsComplexes Interface Water Protein DNA
This work was supported by the Dutch Foundation for Scientific Research (NWO) through a VICI Grant (no 700.56.442) to A.M.J.J.B. and by the WeNMR project (European FP7 e-Infrastructure grant, contract no. 261572, www.wenmr.eu). The national Grid Initiatives of Belgium, France, Italy, Germany, The Netherlands (via the Dutch BiG Grid project), Portugal, Spain, UK, South Africa, Taiwan, and the Latin America GRID infrastructure via the Gisela project are acknowledged for the use of computing and storage facilities. The European Grid Initiative (www.egi.eu) is acknowledged for its support of the WeNMR Virtual Research Community.
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