A unified theory of the B-Z transition of DNA in high and low concentrations of multivalent ions

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 ascribed to the lesser electrostatic free energy of the B form, due to bet ter immersion of the phosphates in the solution. This property was incorpor ated in cylindrical DNA models that were analyzed by Poisson-Boltzmann theo ry. The results are insensitive to details of the models, and in fair agree ment with experiment. In contrast, the Z form of the poly[d(G-m5C)] duplex is stabilized by very small concentrations of magnesium. We now show that t his striking difference is accommodated quantitatively by the same electros tatic theory, without any adjustable parameter. The different responses to magnesium of the methylated and nonmethylated polymers do not come from ste reospecific cation-DNA interactions: they stem from an experimentally deriv ed, modest difference in the nonelectrostatic component of the free energy difference (or NFED) between the Z and B forms. The NFED is derived from ci rcular DNA measurements. The differences between alkaline earth and transit ion metal ions are explained by weak coordination of the latter. The theory also explains the induction of the transition by micromolar concentrations of cobalt hexammine, again without specific binding or adjustable paramete rs. Hence, in the case of the B-Z transition as in others (e.g., the foldin g of tRNA and of ribozymes), the effect of multivalent cations on nucleic a cid structure is mediated primarily by nonspecific ion-polyelectrolyte inte ractions. We propose this as a general rule for which convincing counter-ex amples are lacking.