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

• Published in: Biophysical chemistry Vol. 129; no. 1; pp. 56 - 59
• Main Authors: Kostjukov, V.V., Lantushenko, A.O., Davies, D.B., Evstigneev, M.P.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2007
• Subjects: Aromatic ligand; Base Sequence; Binding Sites; d(GCGAAGC); Daunorubicin - pharmacology; DNA - chemistry; Ethidium - pharmacology; Hot Temperature; Hydrocarbons, Aromatic - chemistry; Hydrocarbons, Aromatic - pharmacology; Mitoxantrone - pharmacology; Molecular dynamics; Nucleic Acid Conformation - drug effects; Nucleic Acid Denaturation - drug effects; Pharmaceutical Preparations - chemistry; Proflavine - pharmacology; Thermal stability; Thermodynamics; Water - chemistry; Water bridges; Molecular dynamics; Water bridges; Aromatic ligand; Thermal stability; d(GCGAAGC)
• ISSN: 0301-4622; 1873-4200
• DOI: 10.1016/j.bpc.2007.05.005

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.