Ion Counting from Explicit-Solvent Simulations and 3D-RISM
Ion Counting from Explicit-Solvent Simulations and 3D-RISM
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DOI：
10.1016/j.bpj.2014.01.021
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发表时间：
2014-02-18
影响因子：
3.4
通讯作者：
Case, David A.
中科院分区：
文献类型：
--
作者：
Giambasu, George M.;Luchko, Tyler;Case, David A.
核酸周围的离子气氛在原子水平上的细节仍然只是部分地被了解。离子计数（IC）实验提供了核酸周围离子气氛的定量测量，因此，是测试定量理论方法的自然途径。在本文中，我们利用分子动力学（MD）模拟、三维参考相互作用位点模型（3D-RISM）、非线性泊松-玻尔兹曼（NLPB）计算和最近的缓冲平衡原子发射光谱测量结果，重复了双链DNA在NaCl（aq）中的IC实验。此外，我们概述了解释IC实验的统计力学基础，并阐明了特定浓度尺度的使用。在接近生理浓度时，MD模拟和3D-RISM估计接近实验结果，但在更高的浓度（>0.7 M）下，两种方法都低估了凝聚阳离子的数量，高估了排除阴离子的数量。DNA电荷对离子和水气氛的影响从表面延伸20-25埃，产生分层密度剖面。总体而言，3d - rism的离子分布与相应的MD模拟相对接近，但凹槽中的Na+结合较少，与磷酸盐的结合更紧密。另一方面，NLPB计算系统地低估了几乎所有浓度下缩合阳离子的数量，并产生了几乎无结构的离子分布，这与MD模拟和3D-RISM产生的结果在质量上不同。这些结果表明，MD模拟和3D-RISM可以进一步发展，为核酸周围离子气氛的表征及其对结构和稳定性的影响提供定量的见解。
The ionic atmosphere around nucleic acids remains only partially understood at atomic-level detail. Ion counting (IC) experiments provide a quantitative measure of the ionic atmosphere around nucleic acids and, as such, are a natural route for testing quantitative theoretical approaches. In this article, we replicate IC experiments involving duplex DNA in NaCl(aq) using molecular dynamics (MD) simulation, the three-dimensional reference interaction site model (3D-RISM), and nonlinear Poisson-Boltzmann (NLPB) calculations and test against recent buffer-equilibration atomic emission spectroscopy measurements. Further, we outline the statistical mechanical basis for interpreting IC experiments and clarify the use of specific concentration scales. Near physiological concentrations, MD simulation and 3D-RISM estimates are close to experimental results, but at higher concentrations (>0.7 M), both methods underestimate the number of condensed cations and overestimate the number of excluded anions. The effect of DNA charge on ion and water atmosphere extends 20-25 angstrom from its surface, yielding layered density profiles. Overall, ion distributions from 3D-RISMs are relatively close to those from corresponding MD simulations, but with less Na+ binding in grooves and tighter binding to phosphates. NLPB calculations, on the other hand, systematically underestimate the number of condensed cations at almost all concentrations and yield nearly structureless ion distributions that are qualitatively distinct from those generated by both MD simulation and 3D-RISM. These results suggest that MD simulation and 3D-RISM may be further developed to provide quantitative insight into the characterization of the ion atmosphere around nucleic acids and their effect on structure and stability.