Biological motion constitutes a key and indispensable element of all biomolecules, as dynamics tightly link spatial architecture with function. Several computational and experimental techniques have been developed to study biomolecular dynamics. Nevertheless, few label-free and atomic or sub-atomic resolution techniques are able to capture biological motions at close to native conditions. Indeed, the only label-free technique giving atomic level access to dynamics from picoseconds down to seconds is nuclear magnetic resonance (NMR) spectroscopy. In this dissertation, I identify the imperfections and inaccuracies accompanying the routine and well-accepted methods of probing protein dynamics via 15N spin relaxation NMR measurements. Subsequently, I propose and develop solutions and experimental approaches to overcome the limitations and eliminate artefacts. The routine procedures applying heavy water as an internal locking standard lead to artifacts in every type of relaxation rate of 15N amides due to reaction with exchangeable deuterons. The deviations from correct values are most pronounced for highly dynamic and exposed protein fragments. I introduce a novel set of directly detected 15N spin relaxation experiments yielding an unprecedent resolution resolving the signal overlap, although of lower sensitivity. I propose a more accurate. Finally, I present how the 15N spin relaxation techniques and improved routines can be applied to understand biological processes that cannot be described without monitoring molecular motions. Using the example of human BTB domains, which are directly linked to human cancer, I demonstrate the ability to detect cryptic binding sites on the surfaces of proteins. The cryptic binding site was verified by a comprehensive NMR-monitored fragment-based screening that revealed a hit-rate only for MIZ1BTB, which was the only protein displaying slow segmental motions. I also managed to track subtle and biologically-relevant dynamic modulations of an exposed H3 histone tail affected by H1 histones or other histone variants. Enhancement of H3 tail dynamics led to increased H3K36 methylation, while restriction of motions resulted in the opposite effect. These observed correlations unequivocally support the essential role of molecular mobility in biological functions.

Cette thèse s'est intéressée aux relations entre les mouvements biologiques et la perception sonore en considérant le cas spécifique des mouvements graphiques et des sons de frottement qu'ils génèrent. L'originalité de ces travaux réside dans l'utilisation d'un modèle de synthèse sonore basé sur un principe perceptif issu de l'approche écologique de la perception et contrôlé par des modèles de gestes. Des stimuli sonores dont le timbre n'est modulé que par des variations de vitesse produites par un geste ont ainsi pu être générés permettant de se focaliser sur l'influence perceptive de cet invariant transformationel. Une première étude a ainsi montré que l'on reconnait la cinématique des mouvements biologiques (la loi en puissance 1/3), et que l'on peut discriminer des formes géométriques simples juste à partir des sons de frottement produits. Une seconde étude a montré l'existence de prototypes dynamiques sonores caractérisant les trajectoires elliptiques, mettant ainsi en évidence que les prototypes géométriques peuvent émerger d'un couplage sensorimoteur. Enfin, une dernière étude a montré qu'une cinématique évoquée par un sonore influence significativement la cinématique et la géométrie d'un geste dans une tâche de reproduction graphique du mouvement d'un point lumineux. Ce résultat révèle l'importance de la modalité auditive dans l'intégration multisensorielle des mouvements continus dans une situation jamais explorée. Ces résultats ont permis le contrôle de modèles de synthèse par des descriptions gestuelles et la création d'outils de sonification pour l'apprentissage de gestes et la réhabilitation d'une pathologie motrice, la dysgraphie. / This thesis focused on the relations between biological movements and auditory perception in considering the specific case of graphical movements and the friction sounds they produced. The originality of this work lies in the use of sound synthesis processes that are based on a perceptual paradigm and that can be controlled by gesture models. The present synthesis model made it possible to generate acoustic stimuli which timbre was directly modulated by the velocity variations induced by a graphic gesture in order to exclusively focus on the perceptual influence of this transformational invariant. A first study showed that we can recognize the biological motion kinematics (the 1/3 power law) and discriminate simple geometric shapes simply by listening to the timbre variations of friction sounds that solely evoke velocity variations. A second study revealed the existence of dynamic prototypes characterized by sounds corresponding to the most representative elliptic trajectory, thus revealing that prototypical shapes may emerged from sensorimotor coupling. A final study showed that the kinematics evoked by friction sounds may significantly affect the dynamic and geometric dimension in the visuo-motor coupling. This shed critical light on the relevance of auditory perception in the multisensory integration of continuous motion in a situation never explored. All of these theoretical results enabled the gestural control of sound synthesis models from a gestural description and the creation of sonification tools for gesture learning and rehabilitation of a graphomotor disease, dysgraphia.