Molecular Interpretation of Temperature-Induced DNA Melting Monitored through Base Dipole Moment Changes as a Surrogate of the Hypochromic Shift.

DNA stability measurements have long been monitored by the hypochromic shift; the increase in UV absorption upon going from native to non-native states is attributed to changes in base transition dipoles arising from altered dipole-dipole interactions. To elucidate the molecular origins of this phenomenon, molecular dynamics simulations with the polarizable Drude force field are used to relate molecular structure to base dipole moments acting as a surrogate for changes in base transition dipoles during melting of the Dickerson-Drew dodecamer. Alterations of base dipoles occur while the DNA duplex is maintained through perturbation of base stacking with the majority of the changes occurring prior to dissociation of the individual strands of the DNA duplex. The results support a three-state melting model involving an intermediate duplex state with perturbation of base stacking and pairing interactions predicted to contribute to the majority of the change in absorption prior to full dissociation of the DNA strands.