PNNL

Abstract

Quantum calculations on duplex DNA trimers were used to model the changes in structure, hydrogen bonding, stacking properties, and electrostatic potential induced by oxidized purine bases and abasic (AP) sites. Results for oxidized purine bases were consistent with experimental data that show small structural and energetic perturbations induced by isolated 8-oxoGC and 8-oxoAT. In contrast, AP sites caused substantial distortions of the DNA backbone that were accompanied by relocation of counterions. New inter- and intra-strand hydrogen bonds formed after removal of a nucleic acid base that significantly affected the energy of AP site and introduced a strong dependence of sequence context. Quantum calculations on small DNA fragments provided starting conformations and force-field parameters for classical molecular dynamics (MD) simulations of radiation-induced single strand breaks that most often combine cleavage of a phosphate-oxygen (PO) bond with an AP site and fully or partially degraded sugar ring. PO bond cleavage increased the freedom in backbone torsion angles, which allowed the broken strand to compress fill the hole in the DNA created by the AP site. Results for strand breaks with a 3’ phosphoglycolate were similar to those with 3’ and 5’ phosphate end groups.