New methods for 1H-detected biomolecular NMR

People working with me on this project at CRMN: C. Ollier (PhD student), Z. Sun (post-doc), S. Medina-Gomez (post-doc), T. Le Marchand (IR CNRS).

Over the past two decades, Magic Angle Spinning (MAS) NMR has evolved into a robust technique in structural biology, complementing solution NMR, X-ray crystallography, and electron microscopy. Initially applied to microcrystalline proteins, MAS NMR now enables three-dimensional structure calculation and dynamic studies of complex assemblies, including amyloid fibrils and viral capsids. The recent introduction of ultra-fast MAS probes (up to 100 kHz) marks a transformative advance, significantly reducing 1H-1H dipolar couplings and, in combination with high magnetic fields, allowing for 1H detection with exceptional resolution and sensitivity. This advance enables the “fingerprinting” of small-to-medium-sized proteins and provides detailed structural data, such as dihedral angles, inter-nuclear proximities, and dynamic parameters.
However, despite these advances, 1H-detected MAS NMR remains a frontier, with applications to biomolecules still in their early stages. Our ongoing efforts are aimed at breaking new ground, from designing pulse sequences that push the limits of resolution, to capturing high-quality internuclear contacts, and pioneering novel methods to uncover molecular motions—particularly those elusive, large-scale conformational changes occurring in the μs–ms range.

See: Andreas et al. Proc Natl Acad Sci USA 2016, 113, 9187; Stanek et al. Angew Chem Int Ed 2016, 55, 15504; Orton et al. Angew Chem Int Ed Engl 2020, 59, 2380; Stanek et al. J Am Chem Soc 2020, 142, 5793; Le Marchand et al. Chem Rev 2022, 122, 9943.