Molecular mechanics simulations on covalent complexes between anthramycin and B DNA.

We present molecular mechanics simulation of the covalent interactions of the potent antitumor antibiotic belonging to the pyrrolo[1,4]benzodiazepine class, anthramycin, with six deoxydecanucleotides, d(GCGCGCGCGC)2, d(G10) X d(C10), d(GCGCGTGCGC) X d(GCGCACGCGC), d(GCGCGAGCGC) X d(GCGCTCGCGC), d(GGGGGAGGGG) X d(CCCCTCCCCC), and d(GGGGGTGGGG) X d(CCCCACCCCC), in their minor grooves. The complexes are characterized by both a network of hydrogen bonds between the drug and the polynucleotide and good packing interactions. The DNA double helix in these complexes shows very minimal distortion, and interactions of the drug with the decanucleotides seem to be not very sensitive to the sequence variation around the site of complex formation. The conformational features in the complexes obtained are generally consistent with the experimentally derived conclusions by recent NMR and 2-D NOE studies.