GRAND-CANONICAL MONTE-CARLO MOLECULAR AND THERMODYNAMIC PREDICTIONS OF ION EFFECTS ON BINDING OF AN OLIGOCATION (L(8+)) TO THE CENTER OF DNA OLIGOMERS

Grand canonical Monte Carlo (GCMC) simulations are reported for aqueous solutions containing excess univalent salt (activities a, = 1.76-12.3 mM) and one of the following species: an octacationic rod-like ligand, L(8+); a B-DNA oligomer with N phosphate charges (8 less than or equal to N less than or equal to 100); or a complex resulting from the binding of L(8+) at the center of an N-mer (24 less than or equal to N less than or equal to 250). Simplified models of these multiply charged species are used in the GCMC simulations to predict the fundamental coulombic contributions to the following experimentally relevant properties: 1) the axial distance over which ligand binding affects local counterion concentrations at the surface of the N-mer; 2) the dependence on N of GCMC preferential interaction coefficients, Gamma(32)(MC) = partial derivative C-3/partial derivative C-2\(a+/-,T), where C-3,and C,are, respectively, the molar concentrations of salt and the multiply charged species (ligand, sa N-mer or complex); and 3) the dependence on N of SaKobs = d In K-obs/d In a+/- = Delta(\Z(j)\ + 2 Gamma(32j)), where K-obs is the equilibrium concentration quotient for the binding of L(8+) to the center of an N-mer and Delta denotes the stoichiometric combination of terms, each of which pertains to a reactant or product J having \Z(j)\ charges. The participation of electrolyte ions in the ligand binding interaction is quantified by the magnitude of SaKobs, which reflects the net (stoichiometrically weighted) difference in the extent of thermodynamic binding of salt ions to the products and reactants. Results obtained here from GCMC simulations yield a picture of the salient molecular consequences of binding a cationic ligand, as well as thermodynamic predictions whose applicability can be tested experimentally. Formation of the central complex is predicted to cause a dramatic reduction in the surface counterion (e.g., Na+) concentration over a region including but extending well beyond the location of the ligand binding site. For binding a cationic ligand, S,K, is predicted to be negative, indicating net electrolyte ion release in the binding process. At small enough N, - SaKobs is predicted to decrease strongly toward zero with decreasing N. At intermediate N, - SaKobs appears to exceed its limiting value as N --> infinity.