Measuring Local Electrostatic Potentials Around Nucleic Acids by Paramagnetic NMR Spectroscopy

Electrostatic potentials around macromolecules in the presence of mobile charges are difficult to assess especially for highly charged systems. Here, we report measurements of local electrostatic potentials around DNA by paramagnetic NMR. Through quantitative analysis of NMR paramagnetic relaxation enhancement arising from positively charged or neutral paramagnetic cosolutes, we were able to determine local electrostatic potentials around ¹H nuclei at >100 sites in major and minor grooves of ¹³C,¹⁵N-labeled 15-bp DNA at 100 mM NaCl. Our experimental electrostatic potential data directly confirmed the Coulombic end effects of DNA. The effective near-surface electrostatic potentials from the NMR data were in good agreement with the theoretical predictions with the Poisson-Boltzmann equation. This NMR method allows for unprecedented experimental investigations into the electrostatic properties of nucleic acids.