Effective interaction between helical bio-molecules

The effective interaction between two parallel strands of helical bio-molecules, such as deoxyribose nucleic acids (DNA), is calculated using computer simulations of the "primitive" model of electrolytes. In particular we study a simple model for B-DNA incorporating explicitly its charge pattern as a double-helix structure. The effective force and the effective torque exerted onto the molecules depend on the central distance and on the relative orientation. The contributions of nonlinear screening by monovalent counterions to these forces and torques are analyzed and calculated for different salt concentrations. As a result, we find that the sign of the force depends sensitively on the relative orientation. For intermolecular distances smaller than $6\AA$ it can be both attractive and repulsive. Furthermore we report a nonmonotonic behaviour of the effective force for increasing salt concentration. Both features cannot be described within linear screening theories. For large distances, on the other hand, the results agree with linear screening theories provided the charge of the bio-molecules is suitably renormalized.Comment: 18 pages, 18 figures included in text, 100 bibliog

Adsorption of mono- and multivalent cat- and anions on DNA molecules

Adsorption of monovalent and multivalent cat- and anions on a deoxyribose nucleic acid (DNA) molecule from a salt solution is investigated by computer simulation. The ions are modelled as charged hard spheres, the DNA molecule as a point charge pattern following the double-helical phosphate strands. The geometrical shape of the DNA molecules is modelled on different levels ranging from a simple cylindrical shape to structured models which include the major and minor grooves between the phosphate strands. The densities of the ions adsorbed on the phosphate strands, in the major and in the minor grooves are calculated. First, we find that the adsorption pattern on the DNA surface depends strongly on its geometrical shape: counterions adsorb preferentially along the phosphate strands for a cylindrical model shape, but in the minor groove for a geometrically structured model. Second, we find that an addition of monovalent salt ions results in an increase of the charge density in the minor groove while the total charge density of ions adsorbed in the major groove stays unchanged. The adsorbed ion densities are highly structured along the minor groove while they are almost smeared along the major groove. Furthermore, for a fixed amount of added salt, the major groove cationic charge is independent on the counterion valency. For increasing salt concentration the major groove is neutralized while the total charge adsorbed in the minor groove is constant. DNA overcharging is detected for multivalent salt. Simulations for a larger ion radii, which mimic the effect of the ion hydration, indicate an increased adsorbtion of cations in the major groove.Comment: 34 pages with 14 figure

Proton equilibria in the minor groove of DNA

Poisson-Boltzmann calculations by Pack and co-workers suggest the presence of regions of increased hydrogen ion density in the grooves of DNA. As an experimental test of this prediction, we have attached proton-sensitive probes, with variable linker lengths, to random-sequence DNA at G sites in the minor groove. The amino groups of beta-alanine, gamma-aminobutyric acid (GABA), and epsilon-aminocaproic acid have been coupled at pH 5, via a formaldehyde link, to the exocyclic amino group of guanine, utilizing a reaction that has been extensively investigated by Hanlon and co-workers. The resulting adducts at pH 5 retained duplex B form but exhibited typical circular dichroism (CD) changes previously shown to be correlated with the presence of a net positive charge in the minor groove. Increases in the solvent pH reversed the CD spectral changes in a manner suggesting deprotonation of the carboxylic acid group of the adduct. These data were used to calculate an apparent pK(a) for the COOH. The pK(a) was increased by 2.4 units for beta-alanine, by 1.7 units for GABA, and by 1.5 units for epsilon-amino caproic acid, relative to their values in the free amino acid. This agrees well with Poisson-Boltzmann calculations and the energy minimization of the structures of the adducts that place the carboxyl groups in acidic domains whose hydrogen ion density is approximately 2 orders of magnitude greater than that of bulk solvent

The effect of a variable dielectric coefficient and finite ion size on Poisson-Boltzmann calculations of DNA-electrolyte systems

The results of variable dielectric coefficient Poisson-Boltzmann calculations of the counter-ion concentration in the vicinity of an all-atom model of the B-form of DNA are presented with an emphasis on the importance of spatial variations in the dielectric properties of the solvent, particularly at the macro-ion-solvent interface. Calculations of the distribution of hard-sphere electrolyte ions of various dimensions are reported. The presence of a dielectric boundary significantly increases the magnitude of the electrostatic potential with a concomitant increase in the accumulation of small counter-ions in the groove regions of DNA. Because ions with radii greater than 2 A have restricted access to the minor groove, the effect there is less significant than it is within the major groove. Changes in the dielectric coefficient for the electrolyte solution, allowing variation from 10 to 25, 40, 60, and 78.5 within the first 7.4 A of the surface of DNA, substantially increases the calculated surface concentration of counter-ions of all sizes. A lower dielectric coefficient near the macro-ion surface also tends to increase the counter-ion density in regions where the electrostatic potential is more negative than -kT. Regardless of the choice of dielectric coefficient, the number of ions in regions where the electrostatic potential is less than -kT remains the same for 0.153 M added 1–1 monovalent electrolyte as for the case without added salt.(ABSTRACT TRUNCATED AT 250 WORDS