On the origin of the decrease in stability of the DNA hairpin d(GCGAAGC) on complexation with aromatic drugs

Molecular dynamics simulations of drug–DNA complexes have been carried out in order to explain the experimentally observed decrease in thermal stability of the DNA hairpin d(GCGAAGC) on binding the aromatic drug molecules, daunomycin, ethidium bromide, novantrone and proflavine. This complexation behavior is in contrast to the stabilizing effect of the same aromatic drug molecules on DNA duplexes. Analysis of the energy parameters and the hydration properties of the complexes shows that the main factor correlating with the decrease in melting temperatures of the drug–hairpin complexes is the number of water bridges, with a reduction of at least 40% on ligand binding