Molecular Modeling Laboratory, Department of Chemistry, Indian Institute of Technology, Kharagpur - 721302, India.
J Chem Phys. 2011 Oct 7;135(13):135101. doi: 10.1063/1.3634004.
Formation of protein-DNA complex is an important step in regulation of genes in living organisms. One important issue in this problem is the role played by water in mediating the protein-DNA interactions. In this work, we have carried out atomistic molecular dynamics simulations to explore the heterogeneous dynamics of water molecules present in different regions around a complex formed between the DNA binding domain of human TRF1 protein and a telomeric DNA. It is demonstrated that such heterogeneous water motions around the complex are correlated with the relaxation time scales of hydrogen bonds formed by those water molecules with the protein and DNA. The calculations reveal the existence of a fraction of extraordinarily restricted water molecules forming a highly rigid thin layer in between the binding motifs of the protein and DNA. It is further proved that higher rigidity of water layers around the complex originates from more frequent reformations of broken water-water hydrogen bonds. Importantly, it is found that the formation of the complex affects the transverse and longitudinal degrees of freedom of surrounding water molecules in a nonuniform manner.
蛋白质-DNA 复合物的形成是生物体内基因调控的重要步骤。该问题的一个重要问题是水在介导蛋白质-DNA 相互作用中所起的作用。在这项工作中，我们进行了原子分子动力学模拟，以探索在与人端粒结合蛋白 1（TRF1）的 DNA 结合域和端粒 DNA 形成的复合物周围不同区域中存在的水分子的非均匀动力学。结果表明，复合物周围的这种非均匀水分子运动与这些水分子与蛋白质和 DNA 形成的氢键的弛豫时间尺度相关。该计算揭示了在蛋白质和 DNA 的结合基序之间存在一部分非常受限的水分子，形成了一个高度刚性的薄层。进一步证明了复合物周围水层的更高刚性源于更频繁地重新形成断裂的水分子氢键。重要的是，发现复合物的形成以非均匀的方式影响周围水分子的横向和纵向自由度。
