<p>In silico ligand docking is a versatile and common technique when predicting ligands and inhibitors for protein binding sites. The various docking programmes aim to calculate binding energies and to predict interactions, thus identifying potential ligands.The currently available programmes lack satisfying means by which to account for structural water molecules which can either mediate protein-ligand contacts or be displaced upon ligand binding. The present project aims to generate data to facilitate the global work of developing scoring functions in docking programmes to account for structural water molecules contribution to ligand binding to fill the said void. This is done by validating the performance of docking using a simple model system (cytochrome C peroxidase (CCP) W191G) containing four well ordered, deeply buried structural water molecules which are known to either interact with a ligand or to be displaced upon ligand binding.Known ligands were docked into eight (crystallographically determined) receptor set-ups comprising the receptor and no, one or two of the water molecules. The performance was validated by comparison of the binding modes of the docked ligands and the crystal structures, comparison of docking scores of the ligands in the different set-ups, enrichment of the ligands from a database of decoys and finally by predicting new ligands from the decoy database. In addition a high resolution crystal structure of CCP W191G in complex with 3-aminopyridine (3AP) was determined in order to resolve ambiguities in the binding mode of this ligand.</p>

Cette étude est basée sur la collection la plus complète d'éclogites cratoniques (> 180 nodules), provenant des cratons sibériens et sud-africains.Les éclogites non-métasomatisés de type IIA sont plus magnésiennes, enrichis en LREE, avec des valeurs de δ18O, de 3,7-7,5 ‰, des anomalies positives en Sr et correspondant à une couche à basse pression-température (PT). La composition de la roche totale est un protolithe basaltique. Les éclogites de type IIB sont plus sodiques et alumineux, appauvris en terres rares, avec des valeurs de δ18O de 2,3-3,6 ‰, correspondant à l'équilibre à haute PT. La composition de la roche totale correspond au protolithe pyroxénitique. Les éclogites à coésite, disthène ou corindon ont des clinopyroxènes riches en jadéite, avec des anomalies positives en Eu et Sr et des grenats riches en grossulaire, avec des anomalies positive en Eu et négatives en Sr. Les estimations de PT indiquent que les éclogites à co-ky-cor ont été équilibrées dans la partie la plus basse de la quille cratonique et la composition de la roche totale correspondant à un protolithe gabbroïque très appauvri, cohérente avec la subduction d'une séquence basaltique à websteritique d'une croûte océanique altérée, appauvrie en éléments incompatibles.L'estimation minimum d'eau dans l'omphacite d'Obnazhennaya est de ~930-1410 ppm d'H20 et pour la roche totale de ~310-890 ppm H2O, significativement supérieures aux péridotites environnantes. Ainsi, les éclogites du manteau peuvent être un important réservoir d'eau à la base de la racine cratonique, avec des conséquences majeures pour la longévité de la quille cratonique, la rhéologie du manteau et pour le cycle global de l'eau. / This study is based on the most complete existing collection of cratonic eclogites (> 180 nodules), from the Siberian and South African cratons. Non-metasomatized Type IIA eclogites are typically more magnesian, LREE-enriched, with δ18O values of 3.7-7.5 ‰, positive Sr anomalies and corresponding to a low pressure-temperature (PT) layer. The whole-rock composition is consistent with a basaltic protolith. Type IIB eclogites are morsodic and aluminous, LREE-depleted, with δ18O values of 2.3-3.6‰, corresponding to equilibrium at high-PT. The whole-rock trace element composition is consistent with a pyroxenitic protolith. Coesite, kyanite and corundum-bearing eclogites ypically have jadeite-rich clinopyroxenes witlpositive Eu and Sr anomalies and grossular-rich gamets with corresponding positive Eu and negative Sr anomalies. PT-estimates indicate coe-kycor-bearing eclogites equilibrated in the lowermost part of the cratonic keel and reconstructed whole-rock trace element composition corresponds to a very depleted gabbroic protolith. This is consistent with the subduction of a hydrothermally altered, basaltic to websteritic sequence of an incompatible-element-depleted oceanic crust.Calculated water content of omphacite is a minmum estima te of ~930-1410 ppm by weight H2O and reconstructed estimates for whole-rock watercontent ~310-890 ppm HO) for the Obnazhennaya eclogites are significantly higher than those of the surrounding peridotites. Thus, mantle eclogite may be an important water reservoir at the base of the cratonic root, with major consequences for cratonic keel, longevity mantle rheology and global water cvcle

In silico ligand docking is a versatile and common technique when predicting ligands and inhibitors for protein binding sites. The various docking programmes aim to calculate binding energies and to predict interactions, thus identifying potential ligands.The currently available programmes lack satisfying means by which to account for structural water molecules which can either mediate protein-ligand contacts or be displaced upon ligand binding. The present project aims to generate data to facilitate the global work of developing scoring functions in docking programmes to account for structural water molecules contribution to ligand binding to fill the said void. This is done by validating the performance of docking using a simple model system (cytochrome C peroxidase (CCP) W191G) containing four well ordered, deeply buried structural water molecules which are known to either interact with a ligand or to be displaced upon ligand binding.Known ligands were docked into eight (crystallographically determined) receptor set-ups comprising the receptor and no, one or two of the water molecules. The performance was validated by comparison of the binding modes of the docked ligands and the crystal structures, comparison of docking scores of the ligands in the different set-ups, enrichment of the ligands from a database of decoys and finally by predicting new ligands from the decoy database. In addition a high resolution crystal structure of CCP W191G in complex with 3-aminopyridine (3AP) was determined in order to resolve ambiguities in the binding mode of this ligand.

Dans le cadre de l’entreposage et du stockage des colis de déchets nucléaires et du transport de combustibles usés, nous nous sommes intéressés par l’étude de la production d’hydrogène de deux produits de corrosion de l’aluminium : l’hydroxyde d’aluminium (Al(OH)3) et l’oxyhydroxyde d’aluminium (AlO(OH)).La production du dihydrogène par irradiation de ces matériaux a été étudiée en fonction de la taille et de la structure que ce soit à température ambiante ou après. Afin d’avoir une meilleur compréhension des mécanismes de production de ce gaz, les défauts créés par irradiation ont été caractérisés en utilisant la Résonnance Paramagnétique Electronique (RPE). Différentes sources d’irradiation ont été utilisées comme le rayonnement Gamma, les électrons accélérés et les ions lourds. Dans un second temps, l’effet de l’hydratation de surface des matériaux a été également étudié. Enfin, l’effet de la présence d’impuretés sur la production de H2 a été brièvement étudié. / Dihydrogen production is a critical issue for the current management of nuclear wastes. One potential source of hydrogen generation is the radiolysis of hydrated mineral phases encountered in the nuclear waste transportation and storage casks. We chose to study aluminum hydroxide (Al(OH)3) (Bayerite) and oxyhydroxides (AlOOH) (Boehmite) as model compounds. The determination of molecular hydrogen production was evaluated with respect to structure and particle size at room temperature and after annealing. In order to have a better understanding of the mechanisms and to identify the precursors of molecular hydrogen, we studied the irradiation defects and their stabilities using Electron Paramagnetic Resonance (EPR). The effect of adsorbed water and structural water on the molecular hydrogen production was studied. Different radiation sources were used such as Gamma radiation, electron beam radiations and heavy ions. In the last part, preliminary results related to the impact of impurities on hydrogen production are presented.