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 aqueou s solutions containing excess univalent salt (activities a, = 1.76-12. 3 mM) and one of the following species: an octacationic rod-like ligan d, L(8+); a B-DNA oligomer with N phosphate charges (8 less than or eq ual to N less than or equal to 100); or a complex resulting from the b inding 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 charge d species are used in the GCMC simulations to predict the fundamental coulombic contributions to the following experimentally relevant prope rties: 1) the axial distance over which ligand binding affects local c ounterion concentrations at the surface of the N-mer; 2) the dependenc e 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 stoichiometri c combination of terms, each of which pertains to a reactant or produc t J having \Z(j)\ charges. The participation of electrolyte ions in th e ligand binding interaction is quantified by the magnitude of SaKobs, which reflects the net (stoichiometrically weighted) difference in th e extent of thermodynamic binding of salt ions to the products and rea ctants. Results obtained here from GCMC simulations yield a picture of the salient molecular consequences of binding a cationic ligand, as w ell as thermodynamic predictions whose applicability can be tested exp erimentally. 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 strongl y toward zero with decreasing N. At intermediate N, - SaKobs appears t o exceed its limiting value as N --> infinity.