Electrostatic, steric, and hydration interactions favor Na⁺ condensation around DNA compared with K⁺

Condensation of monovalent counterions around DNA influences polymer properties of the DNA chain. For example, the Na⁺ ions show markedly stronger propensity to induce multiple DNA chains to assemble into compact structures compared with the K⁺ ions. To investigate the similarities and differences in the sodium and potassium ion condensation around DNA, we carried out a number of extensive all-atom molecular dynamics simulations of a DNA oligomer consisting of 16 base pairs, [d(CGAGGTTTAAACCTCG)]₂, in explicit water. We found that the Na⁺ ions penetrate the DNA interior and condense around the DNA exterior to a significantly larger degree compared with the K⁺ ions. We have provided a microscopic explanation for the larger Na⁺ affinity toward DNA that is based on a combination of steric, electrostatic, and hydration effects. Unexpectedly, we found that the Cl^- co-ions provide more efficient electrostatic screening for the K⁺ ions than for the Na⁺ ions, contributing to the larger Na⁺ condensation around DNA. To examine the importance of the discrete nature of water and ions, we also computed the counterion distributions from the mean-field electrostatic theory, demonstrating significant disagreements with the all-atom simulations. Prior experimental results on the relative extent of the Na⁺ and K⁺ condensation around DNA were somewhat contradictory. Recent DNA compaction experiments may be interpreted to suggest stronger Na⁺ condensation around DNA compared to K⁺, which is consistent with our simulations. We also provide a simple interpretation for the experimentally observed increase in DNA electrophoretic mobility in the alkali metal series, Li⁺ < Na ⁺ < K⁺ < Rb⁺. We compare the DNA segment conformational preferences in various buffers with the proposed NMR models.