Objective
Computational enzyme design challanges our understanding of molecular enzymology and recognition and has previously been used to generate functional biocatalysts for a hand full of reactions. However, thus far all computationally designed enzymes showed low catalytic efficiency when compared to naturally occurring ones. Evolutionary, new enzyme functions are introduced into nature by amino acid sequence optimization. This is facilitated via repurposing the catalytic machinery of an existing active site from an enzyme with a specific function, for a new/different reaction. Here I propose the utilization of already characterized catalytic geometries derived from natural enzymes for computational enzyme design. Using these machineries for the design of non-natural reactions, I want to redesign mono- and dinuclear metalloenzymes for the catalysis of a nucleophilic aromatic substitution reaction. In particular, we want to design an enzyme that catalyzes the dechlorination of the herbicidal compound atrazine, which was shown to accumulate in soil and ground water and was correlated to increased risk of cancer. The project will involve the construction of a structural database exclusively comprising scaffolds of mononuclear zinc enzymes. The rmaining stages will include calculation and construction of a substrate model, which recapitulates the transition state of the reaction, the actual design calculations as well as computational and rational evaluations thereof. Subsequently, the best designs as judged from calculated energy and chemical intuition, will be experimentally tested. Two already established assays to test for atrazine dechlorination activity are available and will be used to complete this task. If necessary, directed evolution methods will be used to enhance the levels of catalytic efficiency of the designed enzymes. During the return phase, structure determination of active designs in an apo and substrate bound form will be performed.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences chemical sciences inorganic chemistry transition metals
- natural sciences mathematics pure mathematics geometry
- natural sciences chemical sciences catalysis biocatalysis
- natural sciences chemical sciences organic chemistry amines
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2012-IOF
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
8010 GRAZ
Austria
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.