Molecular modeling of anthracycline—DNA interaction

Abstract

A series of anthracycline antibiotics, daunomycin, doxorubycin and epirubycin, was investigated by both molecular mechanics and quantum chemistry (semiempirical AM1) methods. The charge distributions used to evaluate the electrostatic contribution to the binding energy were calculated by the semi-empirical AM1 method. In order to evidence the sequence specificity of the drugs, some model single- and double-stranded DNA containing the bases adenine (A), thymine (T), cytosine (C) and guanine (G) in AAAA, TTTT, CCCC, GGGG, ATAT and CGCG sequences were used. In the drug—nucleic acid model complexes the quinone chromophore is intercalated between the base pairs of the DNA helix with the glycoside extended into the minor groove. The results outline the differences in the relative contributions of the electrostatic and van der Waals interactions to the total binding energy.