Salt dependent electrostatic effects play a central role in intermolecular interactions involving nucleic acids. In this paper, the finite-difference solution to the nonlinear Poisson-Boltzmann (NLPB) equation is used to evaluate the salt dependent contribution to the electrostatic binding free energy of theminor groove binding antibiotics DAPI, Hoechst 33258 and netropsin to DNA using detailed molecular structures of the complexes. For each of these systems, a treatment based on the NLPB equation accurately describes the variation of the experimentally observed binding constant with bulk salt concentration. A solvation formalism is developed in which salt effects are described in terms of three free energy contributions: the electrostatic ion-molecule interaction free energy, ΔΔGimo; the electrostatic ion-ion interaction free energy, ΔΔGiio; and the entropic ion organization free energy, ΔΔGorgo. The electrostatic terms, ΔΔGimo and ΔΔGiio, have both enthalpic and entropic components, while the term AΔΔGorgo is purely a cratic entropy. Each of these terms depends significantly on salt dependent changes in the counterion and coion concentrations around the DNA. In each of the systems studied, univalent ions substantially destabilize chargedligand-DNA complexes at physiological salt concentrations. This effect involves a salt dependent redistribution of counterions near the DNA. The free energy associated with the redistribution of counterions upon binding is dominated by the unfavorable change in theelectrostatic ion-molecule interactions, ΔΔGimo, rather than the change in the cratic entropy of ion organization, ΔΔGorgo. In addition, theobserved slope of the salt dependence of the free energy is determined by electrostatic ion-molecule and ion-ion interactions as well as the cratic entropy of ion release. These findings are in contrast to modelsin which the cratic entropy of counterion releasedrives binding.
- Binding energy
- DNA binding