Modelling radiation-induced damage in the lac operator –lac repressor complex. DNA damage: 8-oxoguanine

 Among the DNA lesions induced by ionising radiation, one of the most abundant base modifications is that of guanine (G) into 8-oxo-7-hydro-2′-deoxyguanosine (oxoG). The Escherichia coli lac operator–lac repressor complex bearing one or several oxoG was studied by molecular modelling. The initial structure of the complex was obtained from the Protein Data Bank (1CJG entry – model 1). Systematic replacements of G by oxoG were carried out. Modelling involved energy-minimisation and simulated-annealing techniques using the Amber force field. Depending on its location along the DNA sequence, oxoG induces modifications of the energetic characteristics of the complex, the electrostatic potential distribution on the surfaces of the DNA and of the protein, the DNA and protein conformations and DNA and protein flexibility. In the case of the replacement of G by oxoG at position 8 of the fragment, the most noticeable effects are a 13% decrease in the interaction energy and a 14% reduction in the number of intermolecular hydrogen bonds, all other effects being much weaker. Therefore, we may conclude that the presence of one or several such base modifications is insufficient to account, alone, for the experimental observation of the radiation-induced decrease of lac operator–lac repressor binding extent. Received: 20 July 2000 / Accepted: 5 January 2001 / Published online: 3 April 2001