DNA Vibrational Couplings and Structure

During the past 50 years DNA has been widely studied using FTIR spectroscopy and vibrational circular dichroism (VCD). These techniques have been used to monitor structural transitions, folding kinetics, protein-nucleic acid, and drug-binding interactions. However, the infrared spectral features used to monitor DNA structures are largely empirical in nature, with no fundamental underpinnings linking the secondary structures to the vibrational frequencies. In fact, there are several conflicting models for the structure/frequency relations, leaving the interpretation of DNA/RNA infrared spectroscopy qualitative at best.

Our group has exploited the fact that 2D IR spectroscopy probes the coupling between vibrational modes in addition to the mode frequencies themselves. The coupling appears as cross peaks in the 2D IR spectra (Figure 1, peaks E and E), and provides the additional information necessary for us to quantitatively develop and test coupling models to explain the structure/spectroscopy relationship in DNA.

2D IR spectra of DNA (experimental and simulated)

Figure 1. FTIR and 2D IR experimental and simulated spectra of poly(dG)-poly(dC)-like sequences obtained from our models.

To aid in developing these models, we use a variety of quantum calculations to obtain the transition dipole vectors of the isolated DNA bases and the vibrational couplings between DNA bases. By using this combination of theory and experiment we have now been able to account for the coupling between hydrogen-bonded base pairs observed in the FTIR experiments, shown schematically in Figure 2, as well as the vibrational coupling amongst the stacked bases that give rise to the observed VCD spectra for guanosine/cytosine rich DNA.

Figure 2. Pictoral representation of the nearest neighbor coupling model used to obtain the simulated spectrum presented in Figure 1.

Our results suggest that local-mode coupling is applicable for G/C DNA and RNA sequences, similar to the local mode models that exist for peptides and proteins.