Department of Physics and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
Curr Protein Pept Sci. 2011 Sep;12(6):531-9. doi: 10.2174/138920311796957694.
Protein-DNA interactions are the physical basis of gene expression and DNA modification. Structural models that reveal these interactions are essential for their understanding. As only a limited number of structures for protein-DNA complexes have been determined by experimental methods, computation methods provide a potential way to fill the need. We have developed the DISPLAR method to predict DNA binding sites on proteins. Predicted binding sites have been used to assist the building of structural models by docking, either by guiding the docking or by selecting near-native candidates from the docked poses. Here we applied the DISPLAR method to predict the DNA binding sites for 20 DNA-binding proteins, which have had their DNA binding sites characterized by NMR chemical shift perturbation. For two of these proteins, the structures of their complexes with DNA have also been determined. With the help of the DISPLAR predictions, we built structural models for these two complexes. Evaluations of both the DNA binding sites for 20 proteins and the structural models of the two protein-DNA complexes against experimental results demonstrate the significant promise of our model-building approach.
蛋白质与 DNA 的相互作用是基因表达和 DNA 修饰的物理基础。揭示这些相互作用的结构模型对于理解它们至关重要。由于只有有限数量的蛋白质-DNA 复合物结构通过实验方法确定，因此计算方法提供了一种潜在的方法来满足这一需求。我们开发了 DISPLAR 方法来预测蛋白质上的 DNA 结合位点。预测的结合位点已被用于通过对接来辅助构建结构模型，无论是通过引导对接还是从对接构象中选择接近天然的候选物。在这里，我们将 DISPLAR 方法应用于预测 20 个 DNA 结合蛋白的 DNA 结合位点，这些蛋白的 DNA 结合位点已通过 NMR 化学位移扰动来表征。其中两个蛋白质的 DNA 复合物结构也已确定。在 DISPLAR 预测的帮助下，我们为这两个复合物构建了结构模型。对 20 个蛋白质的 DNA 结合位点和两个蛋白质-DNA 复合物的结构模型进行评估，结果表明我们的建模方法具有很大的潜力。
