Does anthramycin bind to Z-DNA as well as to B-DNA? A molecular mechanics study.

Molecular mechanics simulations have been presented on the covalent complexes between anthramycin and the decanucleotides d(GCGCGCGCGC)2 and d(GCGCGTGCGC).d(GCGCACGCGC) in the novel Z form, with the drug docked in the minor groove. The simulations predict that anthramycin binds to Z-DNA almost as well as it does to B-DNA, but with a few key differences in the structural aspects of binding. In particular, the 5' orientation of the drug is preferred in the Z form, contrasting with the preference for 3' orientation in the B form and the drug has a left-handed twist. While no experimental studies have been published on the binding of pyrrolo(1,4)benzodiazepines to left-handed forms of DNA, the energy refined stereochemically satisfactory models provide valuable information which will hopefully simulate high resolution 2-D NMR/NOE studies in solution.