Aromatic ring flips reveal reshaping of protein dynamics in crystals and complexes

article Aromatic ring flips reveal reshaping of protein dynamics in crystals and complexes epub_ahead yes Lea Marie Becker author 36336939-eb97-11eb-a6c2-c83f1214ca790000-0002-6401-5151 Haohao Fu author Benjamin Tatman author 71cda2f3-e604-11ee-a1df-da10587eda3f Matthias Dreydoppel author Anna Kapitonova author 9fb2a840-89e1-11ee-a8b7-cc5c7ba62471 Daniel Balazs author 302BADF6-85FC-11EA-9E3B-B9493DDC885E0000-0001-7597-043X Ulrich Weininger author Sylvain Engilberge author Christophe Chipot author Paul Schanda author 7B541462-FAF6-11E9-A490-E8DFE56974250000-0002-9350-7606 PaSc department LifeSc department Exploring protein dynamics by solid-state MAS NMR through specific labeling approaches project Protein conformational energy landscapes are shaped not only by intramolecular interactions but also by their environment. In protein crystals and protein–protein complexes, intermolecular contacts alter this energy landscape, but the exact nature of this alteration is difficult to decipher. Understanding how the crystal lattice affects protein dynamics is crucial for crystallography-based studies of motion, yet its influence on collective motions remains unclear. Aromatic ring flips in the hydrophobic core represent sensitive probes of such dynamics. Here, we compare the kinetics of aromatic ring flips in the protein GB1 in crystals, in complex with its binding partner IgG, and in solution, combining advanced isotope labelling with quantitative NMR methods. We show that rings in the core flip nearly a thousand times less frequently in crystals than in solution. Enhanced-sampling molecular dynamics simulations, based on a crystal structure of a GB1 variant reported in this work, reproduce these elevated barriers and reveal how the crystal restrains motions. Springer Nature2026 eng Nature Chemistry 17554330 17554349 4227100610.1038/s41557-026-02155-0 https://research-explorer.ista.ac.at/record/20641 https://research-explorer.ista.ac.at/record/21145 https://research-explorer.ista.ac.at/record/22334 Becker, Lea Marie, et al. “Aromatic Ring Flips Reveal Reshaping of Protein Dynamics in Crystals and Complexes.” Nature Chemistry, Springer Nature, 2026, doi:<a href="https://doi.org/10.1038/s41557-026-02155-0">10.1038/s41557-026-02155-0</a>. Becker LM, Fu H, Tatman B, et al. Aromatic ring flips reveal reshaping of protein dynamics in crystals and complexes. Nature Chemistry. 2026. doi:<a href="https://doi.org/10.1038/s41557-026-02155-0">10.1038/s41557-026-02155-0</a> L.M. Becker, H. Fu, B. Tatman, M. Dreydoppel, A. Kapitonova, D. Balazs, U. Weininger, S. Engilberge, C. Chipot, P. Schanda, Nature Chemistry (2026). Becker, L. M., Fu, H., Tatman, B., Dreydoppel, M., Kapitonova, A., Balazs, D., … Schanda, P. (2026). Aromatic ring flips reveal reshaping of protein dynamics in crystals and complexes. Nature Chemistry. Springer Nature. <a href="https://doi.org/10.1038/s41557-026-02155-0">https://doi.org/10.1038/s41557-026-02155-0</a> Becker LM, Fu H, Tatman B, Dreydoppel M, Kapitonova A, Balazs D, Weininger U, Engilberge S, Chipot C, Schanda P. 2026. Aromatic ring flips reveal reshaping of protein dynamics in crystals and complexes. Nature Chemistry. L. M. Becker et al., “Aromatic ring flips reveal reshaping of protein dynamics in crystals and complexes,” Nature Chemistry. Springer Nature, 2026. Becker, Lea Marie, Haohao Fu, Benjamin Tatman, Matthias Dreydoppel, Anna Kapitonova, Daniel Balazs, Ulrich Weininger, Sylvain Engilberge, Christophe Chipot, and Paul Schanda. “Aromatic Ring Flips Reveal Reshaping of Protein Dynamics in Crystals and Complexes.” Nature Chemistry. Springer Nature, 2026. <a href="https://doi.org/10.1038/s41557-026-02155-0">https://doi.org/10.1038/s41557-026-02155-0</a>. 221052026-06-21T22:03:01Z2026-07-16T12:43:08Z