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Contribution à la compréhension de la chromatographie d'échange d'ions des protéines par un couplage d'approches expérimentales et de simulations moléculaires.

Abstract : The interest for a better understanding of ion-exchange mechanisms at the atomic level has strongly increased over the past decades. Indeed, molecular-level information about physic-chemical mechanisms could help optimizing chromatographic processes for protein purification, which are sub-optimized and still based on empirical methods. Furthermore, behaviors observed in a single-component system cannot be adapted to more complex systems due to the occurrence of phenomena such as protein-protein competition or protein-support interactions. In this context, a promising approach is the use of molecular simulations to investigate local phenomena inside the adsorbents (ion-exchange resin) as a complement to sophisticated experimental techniques, which are difficult to implement and tend to be expensive. Thus, molecular simulations may allow to study protein interactions in its environment, especially with the chromatographic resin, but also to identify possible conformational changes. In this work, the use of molecular simulations is proposed and discussed by comparing simulations against data from macroscopic scale experiments. In particular, ion-exchange equilibrium was studied through adsorption isotherms experiments and application of the Steric Mass Action law in order to evaluate the reliability of this strategy. The first results from molecular simulations obtained with a model system allowed to acquire a molecular insight of retention mechanism of the protein on the chromatographic surface and in particular to identify preferential orientations. Moreover, the comparison of two physical parameters obtained from both approaches (in silico and experiments) showed a good agreement, emphasizing that the use of this kind of numerical method is useful in the field. Modeling the environment effects (pH, ionic strength, competitive proteins) seems also promising, though a deeper investigation and the use of other numerical approaches dedicated to the system complexity should be carried out.
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Submitted on : Wednesday, April 6, 2022 - 3:43:09 PM
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  • HAL Id : tel-03632890, version 1

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Marine Tournois. Contribution à la compréhension de la chromatographie d'échange d'ions des protéines par un couplage d'approches expérimentales et de simulations moléculaires.. Génie des procédés. INSA de Toulouse, 2020. Français. ⟨NNT : 2020ISAT0005⟩. ⟨tel-03632890⟩

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