More Than a Snapshot: Proteins in Motion
A single snapshot is often not enough to understand how biological molecules work. Proteins, for example, can change their shape depending on their environment—sometimes subtly, sometimes dramatically. Researchers from Forschungszentrum Jülich from Helmholtz Information and Heinrich Heine University Düsseldorf have now visualized these shape changes using solid-state NMR spectroscopy. This technique not only captures individual molecular structures, but also entire ensembles of possible states. Their findings provide new insights into protein flexibility and the molecular dynamics involved in neurodegenerative diseases. The study was recently published in the prestigious journal Journal of the American Chemical Society.
(Source: Forschungszentrum Jülich – Press Release)
Capturing Molecular Motion
Traditional structural biology focuses on producing sharp, detailed images of molecules—for example, using X-ray crystallography. However, such methods require molecules to be in a single, fixed conformation. In living cells, this is rarely the case: proteins move, refold, or adopt intermediate forms depending on the conditions.
“A static image is often not enough. Many proteins are flexible, and to truly understand them, we need to consider their movement—the range of shapes they can adopt,” says Professor Henrike Heise of the Institute of Biological Information Processing at Forschungszentrum Jülich.
Frozen Flexibility: What Solid-State NMR Reveals
To capture this flexibility, the research team examined proteins in frozen solution using solid-state NMR spectroscopy—a method also used in materials research. Proteins are flash-frozen in their natural state, preserving all potential folding conformations. These frozen states leave characteristic signatures in the resulting spectra, which can be analyzed and interpreted. The study was made possible by the state-of-the-art equipment at the joint biomolecular NMR center of Heinrich Heine University Düsseldorf and Forschungszentrum Jülich.
The team studied several proteins with different levels of flexibility: a stably folded protein, a naturally flexible intrinsically disordered protein, and a protein that can form amyloid fibrils under certain conditions—a process associated with neurodegenerative diseases.
“One particularly exciting aspect was analyzing the side chain of the amino acid isoleucine,” explains Leonardo Levorin, lead author of the study. “It’s an excellent sensor for molecular dynamics and degrees of freedom at specific sites in a protein.”
By measuring so-called torsion angles—the twisting motion of the side chain—the researchers were able to show how the mobility of specific regions correlates with the protein’s overall structural state.
New Insights into Protein Folding
The findings offer valuable insights into the dynamic behavior of biological molecules, including protein folding and misfolding—phenomena linked to diseases such as Alzheimer’s and Parkinson’s. They also reveal how sensitively certain protein regions respond to their environment—an important consideration for drug development and biopharmaceuticals.
FZJ/A. Tipping, 12.05.2025
Note: The article has been translated from German to English. It is based on a press release from FZJ.
The original press release can be found at:
Proteine in all ihren Gestalten: Forschungsteam macht Formenvielfalt sichtbar (only in german)
The original publication can be found at (Open Access):
Levorin, L., Heise, H., Willbold, D. et al., Capturing conformational ensembles of dynamic proteins by solid-state NMR. J. Am. Chem. Soc. (2025). DOI: https://doi.org/10.1021/jacs.5c04159
Localization in Helmholtz Information:
Helmholtz Information, Program 2: Natural, Artificial and Cognitive Information Processing, Topic 4: Molecular and Celullar Information
Contact:
Prof. Henrike Heise
Institute of Biological Information Processing (IBI)
Structural Biochemistry (IBI-7)
Forschungszentrum Jülich
Phone: +49 2461 61-4658
E-Mail: h.heise@fz-juelich.de
Leonardo Levorin
Institute of Biological Information Processing (IBI)
Structural Biochemistry (IBI-7)
Forschungszentrum Jülich
Phone: +49 2461 61-8069
E-Mail: l.levorin@fz-juelich.de
About Helmholtz Information:
The Research Field “Helmholtz Information” is one of the six research fields of the Helmholtz Association and serves as its digital innovation center. Here, advanced and future computer architectures merge with insights from materials research, data science, and life sciences. Inspired by nature, supported by brain and material research, and enriched by modern approaches in artificial intelligence, experts from the Forschungszentrum Jülich, Karlsruhe Institute of Technology, Helmholtz-Zentrum Hereon, and the Helmholtz-Zentrum Berlin are shaping the digital future in science, business, and everyday life.
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