The sensitivity of the B-Z transition of DNA to multivalent cations in high and low concentrations: A unified electrostatic interpretation

We showed recently that the high-salt transition of poly[d(G-C). poly[d(G-C )] between B-DNA and Z-DNA (at [NaCl] = 2.25 M or [MgCl2] = 0.7 M) can be a scribed to the lesser electrostatic free energy of the B form, due to bette r immersion of the phosphates in the solution. This property was incorporat ed in cylindrical models of B-DNA and Z-DNA which were analyzed by Poisson- Boltzmann theory. The results are insensitive to details of the models, and in fair agreement with experiment. In contrast, the Z form of the poly[d(G-m(5)C)] duplex is stabilized by ver y small concentrations of magnesium. We now show that this phenomenon is ea sily explained by the same electrostatic theory, without any adjustable par ameter. The very different responses to magnesium of the methylated and non -methylated polymers stem from a modest and salt-independent change in the non-electrostatic component of the free energy difference between the Z and B forms. This does not involve any stereo-specific interaction between DNA and the cation. The theory also explains quantitatively the effect of micromolar concentrat ions of trivalent cobalt hexammine on the B-Z transition, and it provides a framework for describing the influence of temperature and of solvent chang es. The difference between the effect of alkaline-earth and transition metal io ns on the transition of poly[d(G-C)] is explained by metal coordination (e. g. to guanine N7). This ion-specificity requires only a modest affinity. Hence, in the case of the B-Z transition as in others (e.g. the folding of tRNA and of ribozymes), the effect of multivalent cations on nucleic acid s tructure is mediated primarily by electrostatic, non-specific interactions. We propose this as a general rule for which convincing counter-examples ar e lacking.