Monte carlo calculations of ion distributions surrounding the oligonucleotide d(ATATATATAT)₂ in the B, A, and wrinkled D conformations

Abstract

We calculated the uni-univalent ion distributions around the oligonucleotide d(AT)5.d(AT)5 in the A, B and wrinkled D conformation using the Metropolis Monte Carlo method. All atoms were included in the oligonucleotide model with partial charges and hard sphere radii assigned to each atom. The univalent counter- and coions were modeled as hard spheres with radius 0.3 nm. The solvent was assigned a dielectric constant of 80, corresponding to a temperature of 298K. The counterion distribution surrounding each of the conformers and the distribution surrounding an impenetrable cylinder, were calculated for four salt concentrations. We found significant counterion density in the major groove of the A DNA while fewer counterions occupied the grooves of B DNA. In the wrinkled D DNA, where groove occupancy is sterically hindered, the ion distributions were identical to the distributions surrounding the impenetrable, cylindrical model. This suggests that excluded volume effects significantly influence the details of the ion distributions near the oligomer, while the detailed charge distributions of the oligomer affects the ion distributions only minimally. Although substantial variation in counterion density was observed near the oligomers of differing conformations, the total number of counterions located within a cylinder surrounding the oligomer bounded radially by 2.4 nm was independent of the conformation of the oligomer. Therefore, for this model system, the local univalent counterion distributions are extremely sensitive to the geometry of the oligonucleotide whereas the extent of neutralization of the oligoanion is insensitive to the conformation of the oligomer.

Both helix topology and counterion distribution contribute to the more effective charge screening in dsRNA compared with dsDNA

“…We attribute this difference to two factors: enhanced counterion association, due to the higher linear charge density of A-form helices, and changes in counterion spatial distribution. In accord with previous studies (16,22), we find that ions penetrate deep inside the major groove of the A-form helix. Since ion size affects the counterion distribution and major groove penetration, we used ion-size corrected Poisson–Boltzmann-based numerical calculations and estimated an ion radius upper bound of 4 Å for effective association of ions.…”

“…The A-form conformation results from a larger lateral and angular displacement of the bases from the helical axis and a shorter rise per base pair, ∼2.8 Å for A-RNA and ∼3.4 Å for B-DNA. Although theoretical (7,21) and computational (22) considerations predict that the increased linear charge density of the A-helix will impact the ion distribution, no measurements comparing the counterion atmosphere around A-RNA and B-DNA helices have been reported.…”

Polyelectrolyte electrostatics: Salt dependence, entropic, and enthalpic contributions to free energy in the nonlinear Poisson–Boltzmann model

“…For example with the +5e/ -5e case, increasing the Debye length to 16 and 32 A decreases the net ion accumulation from 9. In previous uses of the PB equation to assess the degree of counterion binding for comparison with counterion condensation theories, the number of ions within a certain distance of the polyelectrolyte 16,40 or the number in the region where the potential energy of the ion is < kT4' has been suggested. However, the thermodynamic definition of bound ions given by An is preferable since it directly provides the salt dependence of the free energy.…”

Molecular Simulations of DNA Counterion Distributions

“…In some cases, the DNA is presented with all-atom resolution. [39] A detailed study of different ways to mimic helical grooves on DNA was presented by Montoro and Abascal. [13] These authors observed that specific interactions of ions with DNA (soft repulsion potential), the incorporation of the discrete charge distribution, and the grooved nature of the DNA surface may change the ion density profile around DNA considerably (Fig.…”

“…An MC study of a DNA model with an all-atom resolution in a continuum solvent was carried out by Mills et al [39] for different forms of DNA. It was found that the grooved structure of both A-DNA and the B-DNA affects the details of the ion distribution in the center region of the polyion dramatically.…”