THEORETICAL STUDIES OF DRUG-DINUCLEOTIDE INTERACTIONS - EMPIRICAL ENERGY FUNCTION CALCULATIONS ON THE INTERACTION OF ETHIDIUM, 9-AMINOACRIDINE, AND PROFLAVIN CATIONS WITH THE BASE-PAIRED DINUCLEOTIDES GPC AND CPG

Empirical potential function calculations on the interaction of the cationic intercalators ethidium, proflavin and 9-aminoacridine with the base-paired dinucleotide phosphates GpC and CpG are presented. The calculations find reasonable base-paired structures for the GpC- and CpG-intercalator complexes and relative binding energies in the same order as the experimental free energies of association to DNA for ethidium and proflavin. The calculations are consistent with a low activation energy (< 20 kcal/mol) for opening up the dinucleotide phosphate base pair from the DNA structure to one into which the intercalator can fit. The calculations reproduce and rationalize the pyrimidine-3'',5''-purine specificity of these intercalators.