COMPUT. ALDOLASES · Computer aided investigation of aldolase reactivity and stereoselectivity; modelling of new mutated enzymes
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2004-07-01 → 2005-06-30
- EU contribution
- €40,000
- Participants
- 1
- Scheme
- ERG
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Results in brief
Final Activity Report Summary - COMPUT. ALDOLASES (Computer aided investigation of aldolase reactivity and stereoselectivity. Modelling of new mutated enzymes)
The synthesis of new potential drugs is one of the key points in drug development. Traditional synthesis usually has had a hard time generating the complex biomolecules that drugs usually are. On the other hand, enzymes are natural catalysts that can achieve the synthesis of all the huge diversity of molecules found in living beings. The potential to use this ability to synthesise drug candidates is huge, but it is not free of difficulties. One of them is the need to be able to predict and rationalise how the enzymes will behave in front of molecules that are not their natural substrates. The aim of this project was to study the mechanism of an enzyme (an aldolase) that is used by a collaborative group to synthesise potential drugs. By understanding the molecular tricks that the enzyme uses we will be able to predict when it will be more or less proficient when given different molecules. And even better, with the help of molecular biology tools, we can build modified or mutated enzymes that will excel in the synthesis of the particular family of molecules that we are interested in.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS · MADRIDCoordinatorSpain
Links
Data: CORDIS, © European Union