Department of Biotechnology, Indian Institute of Technology Madras, Chennai, Tamilnadu, India.
J Chem Inf Model. 2011 Mar 28;51(3):721-9. doi: 10.1021/ci1003703. Epub 2011 Feb 28.
Protein-DNA recognition plays an essential role in the regulation of gene expression. Understanding the recognition mechanism of protein-DNA complexes is a challenging task in molecular and computational biology. In this work, a scoring function based approach has been developed for identifying the binding sites and delineating the important residues for binding in protein-DNA complexes. This approach considers both the repulsive interactions and the effect of distance between atoms in protein and DNA. The results showed that positively charged, polar, and aromatic residues are important for binding. These residues influence the formation of electrostatic, hydrogen bonding, and stacking interactions. Our observation has been verified with experimental binding specificity of protein-DNA complexes and found to be in good agreement with experiments. The comparison of protein-RNA and protein-DNA complexes reveals that the contribution of phosphate atoms in DNA is twice as large as in protein-RNA complexes. Furthermore, we observed that the positively charged, polar, and aromatic residues serve as hotspot residues in protein-RNA complexes, whereas other residues also altered the binding specificity in protein-DNA complexes. Based on the results obtained in the present study and related reports, a plausible mechanism has been proposed for the recognition of protein-DNA complexes.
蛋白质与 DNA 的识别在基因表达调控中起着至关重要的作用。理解蛋白质-DNA 复合物的识别机制是分子和计算生物学中的一项具有挑战性的任务。在这项工作中，我们开发了一种基于评分函数的方法，用于识别蛋白质-DNA 复合物的结合位点并描绘结合的重要残基。该方法考虑了蛋白质和 DNA 中原子之间的排斥相互作用和距离的影响。结果表明，带正电荷、极性和芳香族残基对结合很重要。这些残基影响静电、氢键和堆积相互作用的形成。我们的观察结果与蛋白质-DNA 复合物的实验结合特异性进行了验证，并且与实验结果非常吻合。蛋白质-RNA 和蛋白质-DNA 复合物的比较表明，DNA 中磷酸原子的贡献是蛋白质-RNA 复合物的两倍。此外，我们观察到带正电荷、极性和芳香族残基在蛋白质-RNA 复合物中充当热点残基，而其他残基也改变了蛋白质-DNA 复合物的结合特异性。基于本研究和相关报告中的结果，提出了一种蛋白质-DNA 复合物识别的合理机制。
