DNA and its counterions: a molecular dynamics study

Abstract

The behaviour of mobile counterions, Na+ and K+, was analysed around a B-DNA double helix with the sequence CCATGCGCTGAC in aqueous solution during two 50 ns long molecular dynamics trajectories. The movement of both monovalent ions remains diffusive in the presence of DNA. Ions sample the complete space available during the simulation time, although individual ions sample only about one-third of the simulation box. Ions preferentially sample electronegative sites around DNA, but direct binding to DNA bases remains a rather rare event, with highest site occupancy values of <13%. The location of direct binding sites depends greatly on the nature of the counterion. While Na+ binding in both grooves is strongly sequence-dependent with the preferred binding site in the minor groove, K+ mainly visits the major groove and binds close to the centre of the oligomer. The electrostatic potential of an average DNA structure therefore cannot account for the ability of a site to bind a given cation; other factors must also play a role. An extensive analysis of the influence of counterions on DNA conformation showed no evidence of minor groove narrowing upon ion binding. A significant difference between the conformations of the double helix in the different simulations can be attributed to extensive alpha/gamma transitions in the phosphate backbone during the simulation with Na+. These transitions, with lifetimes over tens of nanoseconds, however, appear to be correlated with ion binding to phosphates. The ion-specific conformational properties of DNA, hitherto largely overlooked, may play an important role in DNA recognition and binding.

Figure 1

Volume sampled by Na⁺ (dotted line) and K⁺ (solid line) counterions during 50 ns simulation time calculated for all the ions (A) and for the slowest and fastest ions (B).

Figure 2

Counterion distribution around an average DNA structure for Na⁺ (left) and K⁺ (right). The positions shown correspond to roughly 700 to 3500 visits per 1 ų over 50 ns simulation (top 80% of ion density) with red for the highest, white for the medium and blue for the lowest densities.

Figure 3

Minor groove width along the sequence calculated for structures sorted according to their counterion positions from simulation with Na⁺ (A) and K⁺ (B). In green is the average width for structures with ions located in the minor groove of the corresponding base pair, black for ions in the major grove, in blue for ions located between phosphates and average values with standard deviations in red correspond to structures without ions in the given zone. The groove width was measured as a P–P distance reduced by 5.8 Å, the sum of the van der Waals radii of two phosphates.

Figure 4

Counterion distribution in the minor groove of an average DNA using the 1000 narrowest (left) and widest (right) minor groove structures at site C₈–G₁₇ from simulations with Na⁺ (top) and K⁺ (bottom). Phosphates that were used to measure the minor groove width, P₁₀ and P₁₉, are indicated with black spheres.

Figure 5

Minor groove width at level C₈ as a function of simulation time. Average values over 5 ns with standard deviation are given for simulation with Na⁺ (dotted line) and K⁺ counterions (solid line).

Figure 6

Non-canonical α/γ backbone torsions (gauche⁺/trans) as a function of time for simulation with Na⁺ (A) and K⁺ (B); α in solid line and γ in dotted line.