Le mercredi 26 août,  Alexis Marius WANKO NEMBOT présentera l'examen en vue de l’obtention du grade académique de Docteur en Sciences (Collège de doctorat en Biochimie, biologie moléculaire et cellulaire, bioinformatique et modélisation) sous la direction de Christian DAMBLON.

Cette épreuve consistera en la défense publique d’une dissertation intitulée :

« Biomolecular NMR of proteins and peptides : structural analysis and atomic-resolution functional dynamics ».

Le Jury sera composé de :

M. A. MATAGNE (Président), MM. G. BOUVIGNIE (Ecole Normale Supérieure Paris), C. DAMBLON (Promoteur), D. GILIS (ULB), F. KERFF (Secrétaire), J. MARTINS (UGent), A.N. VOLKOV (VUB).

Abstract

Proteins are dynamic molecular entities whose biological functions are governed not only by their three-dimensional structures but also by their intrinsic molecular motions. Nuclear Magnetic Resonance (NMR) spectroscopy provides a unique framework for simultaneously investigating protein structure and dynamics at atomic resolution in solution.
This dissertation exploits advanced NMR methodologies to probe both fast internal motions occurring on the picosecond–nanosecond timescale and low-populated conformational states involved in exchange processes on the microsecond–millisecond timescale. In particular, complementary approaches such as 15N CPMG relaxation dispersion and chemical exchange saturation transfer (CEST) experiments were employed and analyzed to extract exchange parameters. 
These methodologies were applied to a relatively wide range of protein sizes, including enzymatic systems from the TEM β-lactamase family, studied both in their free form (~ 30 kDa) and in complex with a nanobody (~ 45 kDa). The results reveal that ligand binding induces extensive and long-range dynamical rearrangements, demonstrating that nanobody binding modulates the conformational energy landscape of TEM enzymes and highlighting the central role of coordinated effects and conformational dynamics in enzymatic function.
In addition, NMR-based structural studies of a mesophilic cold shock protein CspA (~ 7.5 kDa), combined with NMR molecular dynamics, further illustrate how structure and dynamics are intricately linked to protein adaptation and function.
Overall, this research underscores the necessity of adopting a dynamic view of protein structure and function. By combining advanced NMR relaxation techniques with structural analysis, this dissertation contributes to a deeper understanding of biomolecular dynamics and provides methodological and conceptual insights applicable to a broad range of biological systems.