Competitive interaction of monovalent cations with DNA from 3D-RISM

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.

Quantitative studies of an RNA duplex electrostatics by ion counting

“…Prior studies have shown a strong preferential attraction of cations over the exclusion of anions-24-bp DNA attracted 37 ± 1 cations and excluded 9 ± 1 anions at 10 mM salt concentration, corresponding to 0.804 ± 0.02 attracted cation and 0.195 ± 0.02 excluded anion per charge unit of the double stranded (ds)DNA (20,21,29). Monovalent cation occupancy in the ion atmosphere is insensitive to the cation size across the alkali metal ions Na + , K + , Rb + , and Cs + , contrary to several computational predictions (30)(31)(32)(33). Ion counting also revealed preferential association of divalent cations over monovalent cations around the dsDNA; e.g., with Na + in 4-fold excess of Mg 2+ (20 vs 6 mM), the ion atmosphere nevertheless has 4-fold more Mg 2+ than Na + (20,30).…”

Extracting water and ion distributions from solution x-ray scattering experiments

“…Instead, information about the shape of the ion cloud should be also taken into account. The 3D-RISM model, in its current form, is known to have difficulties with divalent ions, 47,48 perhaps resulting from the lack of polarization effects. 49,50 More work currently is underway to test new ion models in RISM calculations.…”

Theory and Modeling of RNA Structure and Interactions with Metal Ions and Small Molecules

“…The problem is more pronounced for low ion concentration solutions. The difficulty in MD simulation has inspired the development of alternative approaches, such as the modified CC-like and NLPB-like theories (64,96), the three dimensional interaction site model (3D-RISM) (57), and the Tightly Bound Ions model (134, 136). …”

“…Comparisons with SAXS data for the ion distribution support the importance of ion-ion correlation and hydration effects. 3D-RISM is another promising model for solvation and correlation effects based on the density distribution of ions (57). The model solves the Ornstein and Zernike (OZ) integral equation by averaging the solvent degrees of freedom.…”