Molecular mechanical studies of d(CGTACG)2: complex of triostin A with the middle A - T base pairs in either Hoogsteen or Watson-Crick pairing.

Computer graphics model building and molecular mechanical calculations have been carried out on d(CGTACG)2 and its bis-intercalation complexes with triostin A and an N-Me-Ala analogue of triostin A. Two conformations of the DNA have been considered both for the uncomplexed and for complexed nucleic acid: in one the central A - T base pairs are Watson-Crick base paired; in the other they are Hoogsteen base paired. The calculations offer a clear explanation why Hoogsteen base pairing is not favorable in isolated A + T-rich DNA and also suggest reasons why the bis-intercalation of triostin A might help stabilize the neighboring A - T base pairs into a Hoogsteen form. To our knowledge, this is the first study to use molecular mechanical and dynamical methods to investigate the bis-intercalator-DNA complex.