DNA (de)hybridization is the foundation of numerous biological processes and nanotechnology applications. Among the many factors that tune the properties of (de)hybridization, nucleobase sequence is one of the most utilized and studied due to the development of robust nearest-neighbor models to predict (de)hybridization thermodynamics. Nucleobase sequence also reshapes the configurational breadth of the duplex ensemble and dynamics of (de)hybridization, yet these aspects remain poorly understood. Here, we use temperature-jump (T-jump) IR spectroscopy and coarse-grained MD simulations to investigate how nucleobase sequence and modifications tune the dynamics and cooperativity of (de)hybridization. In particular, we have incorporated abasic sites within duplexes of varying sequence to monitor perturbations in local base pairing dynamics and global (de)hybridization due to the removal of a single base. 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 coarse-grained MD simulations reveal dynamic changes on timescales from ns to ms in response to abasic site incorporation. Overall, our results illustrate mechanisms by which nucleobase sequence and nucleobase removal tune and disrupt cooperativity in (de)hybridization and provide new insight into the dynamic contributions of single nucleobases to global conformational changes.

Modulation of DNA duplex dehybridization dynamics by abasic sites uncovered with temperature-jump IR spectroscopy and coarse-grained molecular simulations

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