An effective approach for generating a three-Cys₂His₂ zinc-finger-DNA complex model by docking

Background: Determination of protein-DNA complex structures with both NMR and X-ray crystallography remains challenging in many cases. High Ambiguity-Driven DOCKing (HADDOCK) is an information-driven docking program that has been used to successfully model many protein-DNA complexes. However, a protein-DNA complex model whereby the protein wraps around DNA has not been reported. Defining the ambiguous interaction restraints for the classical three-Cys₂His₂ zinc-finger proteins that wrap around DNA is critical because of the complicated binding geometry. In this study, we generated a Zif268-DNA complex model using three different sets of ambiguous interaction restraints (AIRs) to study the effect of the geometric distribution on the docking and used this approach to generate a newly reported Sp1-DNA complex model.Results: The complex models we generated on the basis of two AIRs with a good geometric distribution in each domain are reasonable in terms of the number of models with wrap-around conformation, interface root mean square deviation, AIR energy and fraction native contacts. We derived the modeling approach for generating a three-Cys₂His₂ zinc-finger-DNA complex model according to the results of docking studies using the Zif268-DNA and other three crystal complex structures. Furthermore, the Sp1-DNA complex model was calculated with this approach, and the interactions between Sp1 and DNA are in good agreement with those previously reported.Conclusions: Our docking data demonstrate that two AIRs with a reasonable geometric distribution in each of the three-Cys₂His₂ zinc-finger domains are sufficient to generate an accurate complex model with protein wrapping around DNA. This approach is efficient for generating a zinc-finger protein-DNA complex model for unknown complex structures in which the protein wraps around DNA. We provide a flowchart showing the detailed procedures of this approach.