A molecular mechanical study of complexes formed between 4-nitroquinoline-N-oxide and dinucleoside phosphates

Molecular mechanical calculations were done on complexes of 4-nitroquinoline-N-oxide (NQO) with various dinucleoside phosphates [(ApT)2, (CpG)2, (GpC)2, and (TpA)2]. Models built using proflavine (uniform C3' endo sugar puckers) and acridine orange (mixed C3' endo (3'-5') C2' endo sugar puckers) dinucleoside phosphate X-ray structures were used in the calculations. Relative binding energies, complex geometries, and various intercalator orientations in the complexes were studied. The results suggest qualitatively different geometries for pyr-(3'-5')-pur and pur-(3'-5')-pyr sequences. Specifically, we find marked distortion in some of the complexes (i.e. there is not a parallel coplanar relationship between the base pairs and intercalator), distortion of the NQO nitro group from planarity in the complexes and mobility of NQO in the intercalation site. We suggest that experimental studies of NQO-dinucleoside phosphate complexes may reveal intercalation complexes which deviate substantially more from a nearly parallel coplanar arrangement of bases and intercalator than has been previously observed.