Does Cation Size Affect Occupancy and Electrostatic Screening of the Nucleic Acid Ion Atmosphere?
Does Cation Size Affect Occupancy and Electrostatic Screening of the Nucleic Acid Ion Atmosphere?
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DOI：
10.1021/jacs.6b04289
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发表时间：
2016-08-31
影响因子：
15
通讯作者：
Herschlag D
中科院分区：
文献类型：
--
作者：
Gebala M;Bonilla S;Bisaria N;Herschlag D
静电对核酸行为的各个方面都很重要，包括它们的折叠、凝聚和与其他分子的结合，这些过程的能量学受到核酸周围离子气氛的深刻影响。考虑到离子大气的高度复杂性和动态性，理解其性质和影响将需要计算建模和实验之间的协同作用。先前的计算模型和实验表明，离子气氛中的阳离子占有率取决于阳离子的大小。然而，计算模型还没有经过独立的测试，实验观察到的影响很小。在这里，我们评估的计算模型的离子大小的影响，通过实验测试从该模型的盲预测，我们提出了额外的实验结果，扩展我们的理解的离子气氛。Giambasu等人开发并实现了DNA和RNA螺旋周围单价阳离子的三维参考相互作用位点（3D-RISM）模型，该模型预测Na+将竞争Cs+1.8-2.1倍;即，在Cs+超过Na+2倍的情况下，离子气氛将含有相等数量的每种阳离子（Nucleic Acids Res.2015，43，8405）。然而，我们的离子计数实验表明，没有显着的偏好Na+超过Cs+。在离子气氛中，Li+比较大的阳离子优先占据约25%，但与现有模型的一般预期相反，其他碱金属离子没有尺寸依赖性。此外，我们跟踪了P4-P6 RNA的折叠，并表明在高浓度下观察到的不同碱金属离子的折叠差异来自阳离子-阴离子相互作用，而不是阳离子尺寸效应。总的来说，我们的研究结果提供了一个关键的测试的计算预测，离子大气特性的基本信息，和参数，这将有助于下一代核酸计算模型的发展。
Electrostatics are central to all aspects of nucleic acid behavior, including their folding, condensation, and binding to other molecules, and the energetics of these processes are profoundly influenced by the ion atmosphere that surrounds nucleic acids. Given the highly complex and dynamic nature of the ion atmosphere, understanding its properties and effects will require synergy between computational modeling and experiment. Prior computational models and experiments suggest that cation occupancy in the ion atmosphere depends on the size of the cation. However, the computational models have not been independently tested, and the experimentally observed effects were small. Here, we evaluate a computational model of ion size effects by experimentally testing a blind prediction made from that model, and we present additional experimental results that extend our understanding of the ion atmosphere. Giambasu et al. developed and implemented a three-dimensional reference interaction site (3D-RISM) model for monovalent cations surrounding DNA and RNA helices, and this model predicts that Na+ would outcompete Cs+ by 1.8–2.1-fold; i.e., with Cs+ in 2-fold excess of Na+ the ion atmosphere would contain an equal number of each cation (Nucleic Acids Res.2015, 43, 8405). However, our ion counting experiments indicate that there is no significant preference for Na+ over Cs+. There is an ∼25% preferential occupancy of Li+ over larger cations in the ion atmosphere but, counter to general expectations from existing models, no size dependence for the other alkali metal ions. Further, we followed the folding of the P4–P6 RNA and showed that differences in folding with different alkali metal ions observed at high concentration arise from cation–anion interactions and not cation size effects. Overall, our results provide a critical test of a computational prediction, fundamental information about ion atmosphere properties, and parameters that will aid in the development of next-generation nucleic acid computational models.
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影响因子：
3.4
作者：
Deng, H;Bloomfield, VA
通讯作者：
Bloomfield, VA
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影响因子：
3.9
作者：
Bisaria N;Herschlag D
通讯作者：
Herschlag D
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作者：
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通讯作者：
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影响因子：
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作者：
Das, R;Mills, TT;Pollack, L
通讯作者：
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影响因子：
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作者：
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通讯作者：
Herschlag, D