Salt-independent counterion kinetics and sub-Poisson number fluctuations in B-DNA from microsecond molecular dynamics

Manning's counterion condensation theory predicts a salt-independent condensed fraction for polyelectrolytes with charge density parameter ξ>1. While the thermodynamic aspects of this prediction have been examined, atomistic tests of whether condensed-ion kinetics are likewise weakly salt-dependent have remained limited. We address this question using 29 independent 1 μs all-atom trajectories of three B-DNA duplexes spanning ionic strengths from 0 to 521 mM. For d(CGCGAATTCGCG)2 (1BNA, x-ray; 16 simulations at six ionic strengths), the Na+ mean residence time in the major groove from Kohlrausch-Williams-Watts stretched-exponential analysis is 511±33 ps with no significant salt dependence (CV = 6.5%, Spearman ρ=-0.15, p=0.77). Similar behavior is observed for the same sequence started from a nuclear magnetic resonance structure (1NAJ, 514±31 ps, CV = 5.9%). A second sequence, d(CCAACGTTGG)2 (5DNB), gives a shorter mean residence time (368±27 ps) and provides supportive but more limited evidence for near-salt-invariance because replicate simulations are not available; independent mean first-passage-time analysis gives 385±13 ps and the same qualitative pattern. While residence times vary little, major-groove occupancy increases 2.4-fold with ionic strength, consistent with increased association but nearly unchanged dissociation kinetics. Ion-number fluctuations are sub-Poisson for all well-sampled conditions, with the grand mean Fano factor F=0.872±0.036, and are less sensitive to salt than occupancy. Together, these results provide atomistic evidence that condensed counterion kinetics in B-DNA depend only weakly on salt, while sequence-dependent differences in absolute residence time lie outside the line-charge approximation of Manning theory.