Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
BMC Bioinformatics. 2010 Jun 18;11:334. doi: 10.1186/1471-2105-11-334.
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.
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.
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.
在许多情况下，使用 NMR 和 X 射线晶体学确定蛋白质-DNA 复合物结构仍然具有挑战性。高模糊度驱动对接（HADDOCK）是一种信息驱动的对接程序，已成功用于模拟许多蛋白质-DNA 复合物。然而，尚未报道蛋白质围绕 DNA 缠绕的蛋白质-DNA 复合物模型。由于结合几何形状复杂，定义围绕 DNA 缠绕的经典三-Cys2His2 锌指蛋白的模糊相互作用约束是至关重要的。在这项研究中，我们使用三种不同的模糊相互作用约束（AIR）生成了 Zif268-DNA 复合物模型，以研究几何分布对对接的影响，并使用这种方法生成了新报道的 Sp1-DNA 复合物模型。
我们根据两个 AIR 生成的复合物模型，每个域中的 AIR 都具有良好的几何分布，在具有环绕构象的模型数量、界面均方根偏差、AIR 能量和原生接触分数方面都是合理的。我们根据 Zif268-DNA 和其他三个晶体复合物结构的对接研究结果，得出了生成三-Cys2His2 锌指-DNA 复合物模型的建模方法。此外，使用这种方法计算了 Sp1-DNA 复合物模型，Sp1 和 DNA 之间的相互作用与先前报道的相互作用一致。
我们的对接数据表明，在三个-Cys2His2 锌指结构域中，每个结构域都有合理的几何分布的两个 AIR 足以生成具有蛋白质环绕 DNA 的准确复合物模型。这种方法对于生成未知复合物结构中具有蛋白质环绕 DNA 的锌指蛋白-DNA 复合物模型非常有效。我们提供了一个流程图，显示了该方法的详细步骤。
