New Screening Method Uses Advanced NMR to Discover Potential Drug Molecules

Published May 22, 2025

NMR data for caffeine interacting with cell membranes

Finding molecules that bind to proteins present in the human body is an essential part of developing new medications. Ordinarily, this is done with “labeled” molecules, but this can be prohibitively expensive, and many molecules can’t be labeled at all. Here, scientists used a specialized nuclear magnetic resonance (NMR) spectroscopy technique to develop a “label-free” approach, significantly expanding the types of molecules that can be studied.

What is the finding

Researchers developed a new way to test if a molecule binds to a protein, which helps in studying biology and developing new medicines. They first proved their method works using known molecules like caffeine and then applied their method to discovering new kinds of molecules that can potentially be further developed into better drugs.

Why is this important?

Most medicines work by attaching to proteins in the body. However, over 4,000 therapeutically-important proteins have no existing drug treatments. Finding molecules that bind to these proteins is crucial for developing new medicines, but traditional methods only work for certain types of molecules. Finding molecules that bind to these proteins is a key part of developing new medications, but conventional methods are limited to molecules that can easily be “labeled” with radioisotopes or fluorescent compounds. This new “label-free” technique allows scientists to study a much wider range of molecules, opening the door to discovering new drugs that were previously impossible to explore.

Who did the research?

Enzo Petracco¹, Guillaume Ferré¹, Ivo Kabelka², Flavio Ballante², Jens Carlsson², Emma Mulry¹, Arka P. Ray¹, James Collins¹, Florent Allais¹, and Matthew T. Eddy¹

¹University of Florida; ²Uppsala University

Why did they need the MagLab?

NMR spectroscopy needs powerful magnets, like those at the MagLab, to work. This study also used a new, special technique called High Resolution Magic Angle Spinning (HRMAS), a technique that yields much higher resolution spectra by spinning the sample inside the magnetic field at a specific angle and frequency using specially-designed equipment that is not commonly available at NMR facilities outside of the MagLab.

Details for scientists

View or download the expert-level Science Highlight, Development of an In Situ G Protein-Coupled Receptor Fragment Molecule Screening Approach with High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance
Read the full-length publication, Development of an In Situ G Protein-Coupled Receptor Fragment Molecule Screening Approach with High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance, in ACS Chemical Biology

Funding

This research was funded by the following grants: K. M. Amm (NSF DMR-2128556); M.T.E. (NIH R35 GM138291); J.C. (Swedish Research Council 2021-04186 and 2021-03464; Olle Engvists 2910154)

For more information, contact Joanna Long.