Electrostatic potentials computed from three-dimensional structures of biomolecules are widely used in molecular biophysics, structural biology, and medicinal chemistry. However, validation of the computed electrostatic potentials through experiments is rare and methodologically limited. Recently, we have developed a unique and powerful nuclear magnetic resonance (NMR) method that allows for straightforward and extensive comparison with electrostatic models for biomolecules and their complexes. This method utilizes paramagnetic relaxation enhancement (PRE) arising from analogous cationic and anionic cosolutes whose spatial distributions around biological macromolecules reflect electrostatic potentials. We demonstrate that this NMR method enables <i>de novo</i> determination of near-surface electrostatic potentials for individual protein residues without using any structural information. We applied the method to ubiquitin and the Antp homeodomain-DNA complex. The experimental data agreed well with predictions from the Poisson-Boltzmann theory. Thus, our experimental results clearly support the validity of the theory for these systems. However, our NMR data also illuminate certain weaknesses of the Poisson-Boltzmann theory. Together with our diffusion-based methods for investigating ions around biomolecules, this NMR method can deepen our understanding of biomolecular electrostatics.

NMR-based measurements of local electrostatic potentials around proteins: Examination of electrostatic theory

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.