Molecular‐mechanical studies of Z‐DNA: A comparison of the structural and energetic properties of Z‐ and B‐DNA

Molecular‐mechanical studies of the left‐handed Z‐DNA polymers have been carried out and the results compared with similar calculations on B‐DNA polymers. We have studied d(CGCGCG) 2 , d(GCGCGC) 2 (and their 5‐methyl cytosine analogs), dG 6 ·dC 6 , d(ATATAT) 2 , and d(TATATA) 2 in both B‐ and Z‐forms. For the left‐handed Z helices, we considered the Z I and Z II model of Quigley and co‐workers [Wang, A. H., Quigley, G. J., Kolpak, F. J., Crawford, J. L., van Boom, J. H., van der Marel, G. & Rich, A. (1979) Nature (London) 282 , 680–686], the actual “Z spermidine” and “Z spermine” structures of Quigley and the model‐built structure of Chandresekharan et al. [Arnott, S., Chandresekharan, R., Bindsall, D. L., Leslie, A. G. W. & Ratliff, R. L. (1980) Nature 283 , 743–745]. The major conclusions of this study are as follows. (1) The stabilization of Z‐DNA relative to B‐DNA occurs as one increases the “effective” dielectric constant or adds counterions, consistent with observations of Z‐DNA only under high salt conditions. (2) The Z II polymer is calculated to be more stable than the Z I polymer. It is not yet clear whether the greater stability of Z II than Z I is a real effect or an artifact caused by the lack of inclusion of specific solvation effects in these calculations. (3) The greater tendency of the 5‐methyl cytosine analog of poly(dG‐dC)·poly(dG‐dC) to undergo the B → Z transition is found in our calculations and is due to destabilizing base–base and base–phosphate interactions, which are greater in the B‐ than in the Z‐form of the 5‐methyl cytosine polymer. (4) There are no large sequence‐dependent effects on the relative stabilities, and the AT polymers are calculated to be as likely to form Z‐helices as the GC polymers. In addition, the relative stability of a nonalternating sequence in the conformation is only slightly less than that found for alternating sequences.