Information-driven protein–DNA docking using HADDOCK: it is a matter of flexibility

By M. V. van Dijk, A. V. van Dijk, V. Hsu, Rolf Boelens, Alexandre M. J. J. Bonvin. 2006

193 citations recorded by the source corpus.

Intrinsic flexibility of DNA has hampered the development of efficient protein−DNA docking methods. In this study we extend HADDOCK (High Ambiguity Driven DOCKing) [C. Dominguez, R. Boelens and A. M. J. J. Bonvin (2003) J. Am. Chem. Soc. 125, 1731–1737] to explicitly deal with DNA flexibility. HADDOCK uses non-structural experimental data to drive the docking during a rigid-body energy minimization, and semi-flexible and water refinement stages. The latter allow for flexibility of all DNA nucleotides and the residues of the protein at the predicted interface. We evaluated our approach on the monomeric repressor−DNA complexes formed by bacteriophage 434 Cro, the Escherichia coli Lac headpiece and bacteriophage P22 Arc. Starting from unbound proteins and canonical B-DNA we correctly predict the correct spatial disposition of the complexes and the specific conformation of the DNA in the published complexes. This information is subsequently used to generate a library of pre-bent and twisted DNA structures that served as input for a second docking round. The resulting top ranking solutions exhibit high similarity to the published complexes in terms of root mean square deviations, intermolecular contacts and DNA conformation. Our two-stage docking method is thus able to successfully predict protein−DNA complexes from unbound constituents using non-structural experimental data to drive the docking.

Subfields: Ecology, Molecular Biology

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Citations in the corpus

Pushing the limits of what is achievable in protein–DNA docking: benchmarking HADDOCK’s performance (2010, methodology): “We focus on the same two questions addressed in the previous work (18): how successful is the method in dealing with conformational changes upon complex formation and how well is it able to identify the correct interaction interfaces? Compared to the three test cases used previously, the 47 test cas”
Crystal structure of the archaeal heat shock regulator from Pyrococcus furiosus: a molecular chimera representing eukaryal and bacterial features. (2007, methodology): “A straight 35 bp B-form DNA with the binding sequence of the aaa+ atpase promoter was modeled and docked onto the surface of the N-terminal part of Phr using the informationdriven docking program HADDOCK.39 In the docking models the two recognition helices insert into the major grooves of adjacent t”
HADDOCK versus HADDOCK: New features and performance of HADDOCK2.0 on the CAPRI targets (2007, background): “For this target, the largest number of three-star predictions (14) was generated at it0.”
Towards the development of universal, fast and highly accurate docking/scoring methods: a long way to go (2008, methodology): “DNA flexibility has been addressed using the HADDOCK programme and semi-flexible refinement using simulated annealing methods following rigid docking (van Dijk et al ., 2006b).”
Recent progress and future directions in protein-protein docking. (2008, background): “…in vacuo SPF Coulomb representation, and the DELPHI linearised Poisson-Boltzmann model [121], respectively, both found that including electrostatics in the scoring function was beneficial in the majority of cases, but worsened the rank of near-native orientations in a significant number of others.”
3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures (2008, methodology): “(Alignment of RNA Tertiary Structures) software uses 3DNA to identify both canonical and noncanonical base pairs for its seed-match construction; (vi) the information-driven protein–DNA docking method HADDOC”
MARTINI-Based Protein-DNA Coarse-Grained HADDOCKing (2019, methodology): “In a previous benchmarking (van Dijk, 2006), acceptable models for this complex were obtained using a two-stage docking protocol in which a library of bent DNA conformations were given as input for the second docking run (a procedure not followed here).”
Structural Basis for Sequence Specific DNA Binding and Protein Dimerization of HOXA13 (2011, methodology): “The structure calculation protocol consists of three stages: rigid-body docking, semi-flexible simulated annealing, and refinement in explicit solvent as described previously [53].”
3D-DART: a DNA structure modelling server (2009, background): “For the same purpose the server can automatically generate a DNA restraint file (16) as an additional feature.”
A protein–DNA docking benchmark (2008, methodology): “We constructed this benchmark as a test base to stimulate developments in the field of protein–DNA docking and will use it in particular for further developing our own protein–DNA docking approach ( 3 ).”