Role of inter and intramolecular interactions in protein-DNA recognition
Role of inter and intramolecular interactions in protein-DNA recognition
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DOI：
10.1016/j.gene.2005.07.022
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发表时间：
2005-12-30
期刊：
影响因子：
3.5
通讯作者：
Sarai, A
中科院分区：
文献类型：
--
作者：
Gromiha, MM;Slebcrs, JG;Sarai, A
蛋白质-DNA识别在基因表达调控中起着重要作用。已知调节蛋白直接通过蛋白质和DNA之间的原子接触和/或间接通过DNA的构象性质识别特定的DNA序列。在这项工作中，我们已经分析了特异性的分子间相互作用的统计分析蛋白质-DNA复合物内的碱基-氨基酸相互作用，以及计算机模拟的碱基-氨基酸相互作用。通过对序列依赖的DNA构象参数和DNA弹性性质的统计分析，研究了分子内相互作用的特异性。这些特异性在大量的蛋白质-DNA复合物的系统比较表明，分子间和分子内的相互作用有助于蛋白质-DNA识别的特异性，其相对贡献取决于蛋白质-DNA复合物。我们证明了分子间和分子内能量的组合导致特异性增强，并且组合能量可以解释碱基突变引起的结合亲和力变化的实验数据。这些结果为蛋白质-DNA识别过程中特异性与结构之间的关系提供了新的见解，这将导致预测特异性蛋白质-DNA结合位点。(C)2005 Elsevier B. V.保留所有权利。
Protein-DNA recognition plays an essential role in the regulation of gene expression. Regulatory proteins are known to recognize specific DNA sequences directly through atomic contacts between protein and DNA, and/or indirectly through the conformational properties of the DNA. In this work, we have analyzed the specificity of intermolecular interactions by statistical analysis of base-amino acid interactions within protein-DNA complexes as well as the computer simulations of base-amino acid interactions. The specificity of the intramolecular interactions was studied by statistical analysis of the sequence-dependent DNA conformational parameters and the elastic properties of DNA. Systematic comparison of these specificities in a large number of protein-DNA complexes revealed that both intermolecular and intramolecular interactions contribute to the specificity of protein-DNA recognition, and their relative contributions vary depending upon the protein-DNA complex. We demonstrated that combination of the intermolecular and intramolecular energies leads to enhanced specificity and the combined energy could explain experimental data on binding affinity changes caused by base mutations. These results provided new insight into the relationship between specificity and structure in the process of protein-DNA recognition, which would lead to prediction of specific protein-DNA binding sites. (C) 2005 Elsevier B.V. All rights reserved.