Objetivo The use of enzymes for asymmetric synthesis is a powerful tool that chemists incorporated in their portfolio during the 90's. The synthesis of natural and non-natural products via aldolases is a good example. However, the enzyme's performance can be different when provided with a substrate different from its natural one. A reasonable solution to this is to modify the enzyme with protein engineering tools to render it more selective towards the desired substrate. Such a goal, however, requires the understanding of the precise mechanism and the role of different aminoacids in the achievement of the stereoselectivity.The present proposal suggests a computational approach to the understanding of some aldolases mechanism in collaboration with an experimental group. The achievement of this goal requires the development of new theoretical techniques as well as the modification of already existing ones, and represents a continuation of the proposer's research career. Emphasis is put on methods that sample the ensemble of transition paths and account for the flexibility of the enzyme.Moreover, this project will shed light to the still controversial subject of how enzymes do their job; introducing novel techniques and computationally studying for the first time some aldolases enzymes. The collaboration with the experimental group will give immediate feedback and, in the end, will lead to a faster and cheaper development of improved enzymes specifically designed for its targets. Ámbito científico medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural scienceschemical sciencescatalysisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesnatural sciencesbiological sciencesmolecular biology Programa(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Tema(s) MOBILITY-4.1 - Marie Curie European Reintegration Grants (ERG) Convocatoria de propuestas FP6-2002-MOBILITY-11 Consulte otros proyectos de esta convocatoria Régimen de financiación ERG - Marie Curie actions-European Re-integration Grants Coordinador CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS Aportación de la UE Sin datos Dirección Calle Serrano 117 MADRID España Ver en el mapa Coste total Sin datos
