Hole Transport Dynamics in Mixed Sequence DNA Can Vary with Salt Concentration: An Experimental and Theoretical Analysis

Long-range hole transport (HT) through DNA is a well-established phenomenon with important applications in the fields of material science, biochemistry, and cell biology. However, the role that the surrounding environment plays in modulating DNA HT dynamics is not well understood and will impact the development of DNA HT theories. Here, we report that varying the bulk salt concentration can affect the dynamics of long-range HT in a mixed sequence DNA duplex. Using a previously described AQ-601 construct, we show that HT to distal guanines is maximal at physiological salt concentrations (100−200 mM), and declines as [NaCl] increases or decreases. Using circular dichroism, we observe that the 601 sequence has the unusual property of underwinding with increasing salt, but the connection of these changes in secondary structure to DNA HT dynamics is not clear. Using all-atom molecular dynamics simulations on decamer duplexes from AQ-601, we show that the changes in HT dynamics do not correlate with salt-dependent fluctuations in local DNA structure and/or electrostatic environment. Since the HT results best correlate with known changes in oxygen diffusion rates vs [NaCl], the rate of hole trapping, involving reaction of the guanine radical cation with oxygen species, appears to control the DNA HT dynamics in this duplex.