Abstract
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.
Highlights
The large negative charge inherent to nucleic acids requires stabilization by a neutralizing ion atmosphere that contains territorial and site-bound cations and excludes anions
We examined the ability of non-linear Poisson–Boltzmann equation (NLPB), 3D-RISM and Molecular dynamics (MD) simulation to reproduce ion counting (IC) results for single-component (NaCl) solutions, as well as compared the predicted ion distributions from the different methods [36]
The presence of the nucleic acid leads to an unequal distribution of ions and water across the membrane that can be expressed as a preferential interaction parameter [22]: DNA,X =
Summary
The large negative charge inherent to nucleic acids requires stabilization by a neutralizing ion atmosphere that contains territorial and site-bound cations and excludes anions. Several extensions of NLPB have been made to include specific ion size effects [18,23,24,25,26] and more advanced models based on densityfunctional theory of liquids or Monte Carlo simulations were shown to effectively treat ion–ion correlations and have been applied to examine the ion environment around nucleic acids [27,28,29,30,31,32,33,34]. These models demonstrate that explicit consideration of ion size effects and ion–ion correlations lead to significant deviations from the spatial distribution of ions relative to conventional NLPB calculations especially near a charged surface
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