Competitive interaction of monovalent cations with DNA from 3D-RISM.
Competitive interaction of monovalent cations with DNA from 3D-RISM.
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DOI：
10.1093/nar/gkv830
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发表时间：
2015-09-30
影响因子：
14.9
通讯作者：
York DM
中科院分区：
文献类型：
--
作者：
Giambaşu GM;Gebala MK;Panteva MT;Luchko T;Case DA;York DM
核酸周围离子气氛的组成会影响它们的折叠、缩合和与其他分子的结合。因此，对离子大气的形成和改变离子条件时的热力学后果进行预测性的洞察是至关重要的。迈向这一目标的早期步骤是将计算模型与定量实验测量结果进行基准比较。在这里，我们测试了三维参考相互作用位置模型(3D-RISM)再现从混合碱氯化物和dsDNA的离子计数(IC)实验中确定的择优相互作用参数的能力。对于盐浓度&200 mm，计算与实验吻合得很好，并捕捉到了观察到的趋势，即DNA周围的阳离子积累程度与其离子大小成反比。离子分布表明，较小的、更具竞争性的阳离子在磷酰基附近积累的程度更大，深入到沟槽中。与实验一致，计算得到的离子分布不随顺序变化，但沟槽中的离子分布与顺序和离子大小有关。对其他核酸构象的计算表明，线电荷密度的变化对阳离子竞争的程度影响不大。
The composition of the ion atmosphere surrounding nucleic acids affects their folding, condensation and binding to other molecules. It is thus of fundamental importance to gain predictive insight into the formation of the ion atmosphere and thermodynamic consequences when varying ionic conditions. An early step toward this goal is to benchmark computational models against quantitative experimental measurements. Herein, we test the ability of the three dimensional reference interaction site model (3D-RISM) to reproduce preferential interaction parameters determined from ion counting (IC) experiments for mixed alkali chlorides and dsDNA. Calculations agree well with experiment with slight deviations for salt concentrations >200 mM and capture the observed trend where the extent of cation accumulation around the DNA varies inversely with its ionic size. Ion distributions indicate that the smaller, more competitive cations accumulate to a greater extent near the phosphoryl groups, penetrating deeper into the grooves. In accord with experiment, calculated IC profiles do not vary with sequence, although the predicted ion distributions in the grooves are sequence and ion size dependent. Calculations on other nucleic acid conformations predict that the variation in linear charge density has a minor effect on the extent of cation competition.