Molecular dynamics simulations of excimer forming (+)-anti-BPDE-DNA adducts in aqueous solution

The chemical carcinogen (+)-anti BPDE preferentially binds covalently to the guanine base in the minor groove of DNA. Fluorescence spectroscopic studies have shown that the BPDE molecules bound to DNA can interact in their photo-excited state giving strong excimer fluorescence when bound to poly(dGdC).poly(dGdC). It was suggested that the formation of such excited state complexes is most probable when the two (+)-anti-BPDE bind to guanines of adjacent base pairs on the two different strands of the DNA. In the present work a model for such an excimer forming DNA-BPDE double adduct system has been constructed and shown to be stable over a 300 ps molecular dynamics simulation in a water box. The model is a d(CG)3.d(CG)3 molecule with two BPDE molecules bound to the guanines at the 4th position on each strand, located in the minor groove and each oriented towards the 5' end of the modified strand, respectively. The results of 300 ps MD simulation show that the two BPDE chromophores exhibited on the average a relative geometry favourable for excimer formation. The local structure at the adduct position was considerably distorted and the helix axis was bent. The modified bases were found to be paired through a stable single non-Watson Crick type of hydrogen bond.