Characterizing the Impact of Abasic Sites on Sequence-Dependent DNA Duplex Dehybridization with Temperature-Jump IR Spectroscopy and Coarse-Grained Molecular Simulation

The biological responsibilities and recent nanotechnology applications of DNA often rely on dynamic interactions between oligonucleotides. The binding affinity and kinetics of (de)hybridization are most commonly tuned by nucleobase sequence due to the development of robust models of two-state duplex (D)-to-single-strand (S) thermodynamics. Nucleobase sequence also impacts the configurational breadth of the duplex ensemble and dynamics of (de)hybridization, yet the details of these effects remain poorly understood. We are studying how the cooperativity and time-dependent properties of the DNA D-to-S transition depend on nucleobase sequence using temperature-jump (T-jump) IR spectroscopy and MD simulations. We are currently investigating how removing specific nucleobases (abasic site) alters (de)hybridization behavior in oligonucleotides of varying sequence. Incorporation of an abasic site reshapes the free energy landscape of the DNA duplex, but does so in a position- and sequence-dependent manner. T-jump experiments and MD simulations reveal how DNA (de)hybridization dynamics change on timescales from ns to ms in response to abasic site incorporation. Overall, our results provide insight into the contribution of single specific nucleobases to the global process of duplex (de)hybridization.