The role of correlation and solvation in ion interactions with B-DNA

Abstract: The ionic atmospheres around nucleic acids play important roles in biological function. Large-scale explicit solvent simulations coupled to experimental assays such as anomalous small-angle X-ray scattering (ASAXS) can provide important insights into the structure and energetics of such atmospheres but are time- and resource-intensive. In this paper, we use classical density functional theory (cDFT) to explore the balance between ion-DNA, ion-water, and ion-ion interactions in ionic atmospheres of RbCl, SrCl$_2$, and CoHexCl$_3$ (cobalt hexammine chloride) around a B-form DNA molecule. The accuracy of the cDFT calculations was assessed by comparison between simulated and experimental ASAXS curves, demonstrating that an accurate model should take into account ion-ion correlation and ion hydration forces, DNA topology, and the discrete distribution of charges on DNA strands. As expected, these calculations revealed significant differences between monovalent, divalent, and trivalent cation distributions around DNA. About half of the DNA-bound Rb$^+$ ions penetrate into the minor groove of the DNA and half adsorb on the DNA strands. The fraction of cations in the minor groove decreases for the larger Sr$^{2+}$ ions and becomes zero for CoHex$^{3+}$ ions, which all adsorb on the DNA strands. The distribution of CoHex$^{3+}$ ions is mainly determined by Coulomb and steric interactions, while ion-correlation forces play a central role in the monovalent Rb$^+$ distribution and a combination of ion-correlation and hydration forces affect the Sr$^{2+}$ distribution around DNA.