Objective
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.
Fields of science
Call for proposal
FP6-2002-MOBILITY-11
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Funding Scheme
ERG - Marie Curie actions-European Re-integration GrantsCoordinator
MADRID
Spain