February 21, 2026
View Full PaperBPS2026 - Integrating 19F restraints for structural biology by magic angle spinning NMR spectroscopy
Key Points
- This research aims to improve the structural analysis of proteins and biological assemblies using advanced NMR techniques.
- Utilized 19F high-frequency magic angle spinning NMR
- Implemented dynamic nuclear polarization approaches
- Analyzed protein assemblies and formulations at natural abundance
- Recorded NMR spectra from nanomole-quantities of proteins in mammalian cells
- Achieved over 35-fold signal enhancements in NMR spectra
- Obtained high signal-to-noise ratio MAS NMR spectra within minutes
- Acquired high-resolution two-dimensional dipolar correlation spectra
- Demonstrated effective probing of protein structure and dynamics in native-like environments
Abstract
We will present recent results establishing 19 F high-frequency (40–110 kHz) magic angle spinning (MAS) NMR and dynamic nuclear polarization (DNP) approaches that overcome sensitivity and resolution bottlenecks in atomic-level characterization of large biological assemblies, pharmaceutical formulations at natural abundance, and proteins in their natural cellular milieus. We will introduce 19 F DNP-enhanced MAS NMR spectroscopy in protein assemblies and proteins in mammalian cells. We will demonstrate that with very large, over 35-fold signal enhancements afforded by these experiments, high signal-to-noise ratio MAS NMR spectra on nanomole-quantities of proteins in cells can be recorded in only minutes, and two-dimensional dipolar correlation spectra with remarkable resolution are obtained. This work paves the way for 19 F DNP-enhanced MAS NMR applications in cellular milieus, for probing protein structure, dynamics and ligand interactions in native-like environments.