The affinity of molecular ions for DNA structures is determined by solvent accessible surface area
The affinity of molecular ions for DNA structures is determined by solvent accessible surface area
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分子离子对 DNA 结构的亲和力由溶剂可及表面积决定
DOI：
10.1021/jp505107g
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发表时间：
2014
期刊：
影响因子：
3.3
通讯作者：
and N. Sugimoto
中科院分区：
文献类型：
--
作者：
M. Nakano;H. Tateishi-Karimata;S. Tanaka;and N. Sugimoto
Hoogsteen碱基对和DNA三链体结构被认为在细胞过程中起重要作用，尽管这些结构比Watson-Crick碱基对的双链体少。分子离子明显影响体内DNA结构的稳定性;然而，其机制尚不清楚。在这里，我们研究了钠离子，胆碱离子，四甲基铵离子对DNA三链体的分子动力学模拟的影响。我们发现，非极性的相互作用，这是与货车的范德华相互作用，和溶剂可及的表面积比极性或静电相互作用更重要，在确定的DNA沟区的分子阳离子的亲和力。由于最佳地适合在DNA沟内的阳离子的自由能增益大于由于脱水效应的自由能损失。阳离子的形状互补的一个特定的DNA凹槽配置稳定的三链体形成，但阳离子干扰DNA碱基之间的氢键是不稳定的。分子阳离子的这些稳定和去稳定机制也适用于由沃森-克里克碱基对组成的DNA双链体。阳离子与DNA结构相互作用的分子水平观点将指导DNA装置、基于DNA的药物和遗传疗法的设计。
It is considered that Hoogsteen base pairs and DNA triplex structures play important roles in cellular processes even though these structures are less than duplexes of Watson–Crick base pairs. Molecular ions clearly affect the stability of DNA structures in vivo; however, the mechanisms are unknown. Here, we investigated the effects of sodium ions, choline ions, and tetramethylammonium ions on DNA triplexes using molecular dynamics simulations. We found that nonpolar interactions, which are associated with van der Waals interactions, and solvent-accessible surface area were more important than polar or electrostatic interactions in determining the affinity of a molecular cation for the DNA groove areas. The free energy gain due to a cation that fit optimally within a DNA groove was larger than the free energy loss due to the effect of dehydration. Cations with shapes complementary to that of a particular DNA groove configuration stabilized triplex formation, but cations that disturbed hydrogen bonds between DNA bases were destabilizing. These stabilizing and destabilizing mechanisms of molecular cations were also applicable to a DNA duplex composed of Watson–Crick base pairs. The molecular-level view of cation interactions with DNA structures will guide the design of DNA devices, DNA-based drugs, and genetic therapies.