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Functional dynamics of biomolecules

Functional dynamics of biomolecules

Staff:

Michel Sliwa
Marten Vos

Post-doc:

Amira Gharbi

Research topics:

Protein functioning relies on their capacity to efficiently adopt distinct configurations. Our research concerns the internal dynamics associated with these specific changes, in particular in proteins involved in catalysis, signaling and engineered photoswitches. The fastest and most specific changes take place on the timescale of the internal protein vibrations. Therefore we employ and develop femtosecond spectroscopic techniques to probe these motions in real time. Our efforts to get detailed insight in the dynamics on a molecular level include combining experimental studies and molecular dynamics simulations. 

These studies rely on triggering protein dynamics using short visible light pulses. Therefore we investigate systems harboring chromophores, including flavin, heme, Fe-S center, retinal, carotenoid and chromophores constituted by post-translationally modified amino-acids. 

Present projects include:

Photocatalytic mechanism of flavoenzyme Fatty Acid Photodecarboxylase  (FAP).

Photodissociation of the charge transfer complex between the flavoprotein MSOX and its MTA inhibitor and its possible photoswitching applications (ANR PhotoCT, 2024-2027).

Signaling mechanism of Orange Carotenoid Protein (OCP) (ANR DynOCP)

Photoswitching of the retinal protein Archearhodopsin-3 (ANR UltrAerchea)

Mechanism of reversibly switchable fluorescence proteins

Much work is developed along with other themes in our lab, in particular  "Adaptive molecular mechanisms in microbial systems" and "Coherent spectroscopy and coherent control in biological systems", and in addition with a number of external collaborations.

 

 

Photocycle of Fatty Acid Photodecarboxylase (FAP). See Sorigué, D. et al, (2021) Science 372, eabd5687

 

Photoswitching in the MSOX-MTA complex. See  Zhuang, B. & Vos, M.H. (2022) J. Am. Chem. Soc. 144, 11569-11573

Selected recent publications:


Zhuang, B., Ramodiharilafy, R., Aleksandrov, A., Liebl, U. & Vos, M.H. (2025) Mechanism of Ultrafast Flavin Photoreduction in the Active Site of Flavoenzyme LSD1 Histone Demethylase, Chem. Sci. 16, 338-344

Aleksandrov, A., Bonvalet, A., Müller, P., Sorigué, D., Beisson, F., Antonucci, L., Solinas, X., Joffre, M. & Vos, M.H. (2024) Catalytic Mechanism of Fatty Acid Photodecarboxylase: on the Detection and Stability of the Initial Carbonyloxy Radical Intermediate, Ang. Chem. Int. Ed. 63, e202401376

Vos, M.H., Salman, M. & Liebl,U. (2022) Early processes in heme-based CO-sensing proteinsFront. Mol. Biosci. 9, 1046412

Zhuang, B. & Vos, M.H. (2022) Photoswitching Behavior of Flavin–Inhibitor Complex in a Nonphotocatalytic Flavoenzyme, J. Am. Chem. Soc. 144, 11569-11573

Zhuang, B., Liebl, U. & Vos, M.H. (2022) Flavoprotein photochemistry: fundamental processes and photocatalytic perspectives, J. Phys. Chem. B 126, 3199-3207

Zhuang, B., Ramodiharilafy, R., Liebl, U., Aleksandrov, A. & Vos, M.H. (2022) Ultrafast Photooxidation of Protein-bound Anionic Flavin Radical, Proc. Natl. Acad. Sci. USA 119, e2118924119

Sorigué, D., Hadjidemetriou, K., Blangy, S., Gotthard, G., Bonvalet, A., Coquelle, N., Samire, P., Aleksandrov, A., Antonucci, L., Benachir, A., Boutet, S., Byrdin, M., Cammarata, M., Carbajo, S., Cuiné, S., Doak, R.B., Foucar, L., Gorel, A., Grünbein, M., Hartmann, E., Hienerwadel, R., Hilpert, M., Kloos, M., Lane, T. J., Légeret,  B., Legrand, P., Li-Beisson, Y., Moulin, S., Nurizzo, D., Peltier, G., Schirò, G., Shoeman, R.L., Sliwa, M., Solinas, X., Zhuang, B., Barends, T.R.M., Colletier, J.-P., Joffre, M., Royant, A., Berthomieu, C., Weik, M., Domratcheva, T., Brettel, K., Vos, M.H., Schlichting, I., Arnoux, P., Müller, P. & Beisson, F. (2021) Mechanism and dynamics of fatty acid photodecarboxylase, Science 372, eabd5687