Electrostatic free energies carry structural information on nucleic acid molecules in solution

Over the last several decades, a range of experimental techniques from x-ray crystallography and atomic force microscopy to nuclear magnetic resonance and small angle x-ray scattering have probed nucleic acid structure and conformation with high resolution both in the condensed state and in solution. We present a computational study that examines the prospect of using electrostatic free energy measurements to detect 3D conformational properties of nucleic acid molecules in solution. As an example, we consider the conformational difference between A- and B-form double helices whose structures differ in the values of two key parameters-the helical radius and rise per basepair. Mapping the double helix onto a smooth charged cylinder reveals that electrostatic free energies for molecular helices can, indeed, be described by two parameters: the axial charge spacing and the radius of a corresponding equivalent cylinder. We show that electrostatic free energies are also sensitive to the local structure of the molecular interface with the surrounding electrolyte. A free energy measurement accuracy of 1%, achievable using the escape time electrometry (ETe) technique, could be expected to offer a measurement precision on the radius of the double helix of approximately 1 angstrom. Electrostatic free energy measurements may, therefore, not only provide information on the structure and conformation of biomolecules but could also shed light on the interfacial hydration layer and the size and arrangement of counterions at the molecular interface in solution. (C) 2022 Author(s).

Automated summary

This study presents a computational investigation on using electrostatic free energy measurements to detect the 3D conformational properties of nucleic acid molecules in solution. The results indicate that electrostatic free energy measurements can not only describe structural differences but also provide information on the local structure of the molecular interface.