Why Na+ has higher propensity than K+ to condense DNA in a crowded environment

Abstract

AbstractExperimentally, in the presence of crowding agent polyethylene glycol (PEG), sodium ions compact double-stranded DNA more readily than potassium ions. Here we have used molecular dynamics simulations and the “ion binding shells model” of DNA condensation to provide an atomic level picture that explains the observed variations in condensation of short (25 base pairs) DNA duplexes in solutions containing different monovalent cations and PEG; several predictions are made. In general, there are two major modes (shells) of ion binding to DNA, internal and external, distinguished by the proximity of bound ions to the helical axis. Externally bound ions contribute the most to the ion-induced aggregation of DNA duplexes. The simulations reveal that for two adjacent DNA duplexes, as well as for a single DNA duplex, the number of externally bound Na+ions is larger than the number of K+ions over a wide range of NaCl and KCl concentrations in the presence of PEG, providing a qualitative explanation for the higher propensity of sodium ions to compact DNA under crowded conditions. The qualitative picture is confirmed by an estimate of the corresponding free energy of DNA aggregation in the presence of different ions: the aggregation free energy is at least 0.2kBTper base pair more favorable in solution with NaCl than with KCl, at the same ion concentration. The estimated attraction free energy of DNA duplexes in the presence of Na+depends on the DNA sequence noticeably: we predict that AT-rich DNA duplexes are more readily condensed than GC-rich ones in the presence of Na+. The sequence dependence of the DNA aggregation propensity is nearly absent for K+. Counter-intuitively, the addition of a small amount of crowding agent with high affinity for the specific condensing ion may lead to the weakening of the ion-mediated DNA-DNA attraction, shifting the equilibrium away from the DNA condensed phase.