Sequence-dependent DNA deformability studied using molecular dynamics simulations.
Sequence-dependent DNA deformability studied using molecular dynamics simulations.
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DOI：
10.1093/nar/gkm627
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发表时间：
2007
影响因子：
14.9
通讯作者：
Sarai A
中科院分区：
文献类型：
--
作者：
Fujii S;Kono H;Takenaka S;Go N;Sarai A
蛋白质不仅通过氨基酸和碱基之间的直接接触识别特定的DNA序列，而且还间接基于DNA的序列依赖性构象和变形性（间接读出）。我们使用分子动力学模拟来分析夹在CGCG序列之间的所有136个可能的四聚体序列的序列依赖性DNA构象。通过模拟得到的二聚体台阶的变形能力与晶体结构一致。模拟结果进一步表明，四聚体的构象和变形能力高度依赖于侧翼碱基对。xATx四聚体的构象显示出最大的刚性，不受侧翼碱基对的影响，而xYRx相反显示出最大的灵活性，并根据两端的碱基对改变其构象，这表明具有相同中心二聚体的四聚体可以显示出不同的变形性。这些结果表明，单独的二聚体步骤的分析可能会忽略DNA的一些构象特征，并提供洞察蛋白质-DNA识别过程中的间接读出机制。此外，DNA构象和变形性的序列依赖性可用于估计间接读出对蛋白质-DNA识别的特异性以及核小体定位和核酸的大规模行为的贡献。
Proteins recognize specific DNA sequences not only through direct contact between amino acids and bases, but also indirectly based on the sequence-dependent conformation and deformability of the DNA (indirect readout). We used molecular dynamics simulations to analyze the sequence-dependent DNA conformations of all 136 possible tetrameric sequences sandwiched between CGCG sequences. The deformability of dimeric steps obtained by the simulations is consistent with that by the crystal structures. The simulation results further showed that the conformation and deformability of the tetramers can highly depend on the flanking base pairs. The conformations of xATx tetramers show the most rigidity and are not affected by the flanking base pairs and the xYRx show by contrast the greatest flexibility and change their conformations depending on the base pairs at both ends, suggesting tetramers with the same central dimer can show different deformabilities. These results suggest that analysis of dimeric steps alone may overlook some conformational features of DNA and provide insight into the mechanism of indirect readout during protein–DNA recognition. Moreover, the sequence dependence of DNA conformation and deformability may be used to estimate the contribution of indirect readout to the specificity of protein–DNA recognition as well as nucleosome positioning and large-scale behavior of nucleic acids.
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