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Content archived on 2024-05-27

Computational Exploration of Directed Evolution rules for tuning enzymatic activities

Objective

Biocatalysis is based on the application of natural catalysts for new purposes, for which the enzymes were not designed. Although the first examples of biocatalysis were reported more than a century ago, biocatalysis was revolutionized after the discovery of an in vitro version of Darwinian evolution called Directed Evolution (DE). Despite the recent advances in the field, major challenges remain to be addressed. Up to date, the best experimental approach consists of creating multiple mutations simultaneously but limit the choices using statistical methods. Still, tens of thousands of variants need to be tested experimentally. In addition to that, little information is available as to how these mutations lead to enhanced enzyme proficiency. Significant advances in computational tools have enabled the de novo design of enzymes catalyzing unnatural reactions making use of the so-called inside-out computational protocol developed by the groups of Prof. Baker and Prof. Houk. Despite the initial computational successes, the most active computationally designed enzymes still perform quite poorly in comparison with the natural and DE-engineered enzymes. This project aims to computationally unveil the molecular basis of improved catalysis achieved by Directed Evolution. In particular, quantum mechanics, Molecular Dynamics simulations, and QM/MM strategies will be used to study some selected DE-engineered enzymes. The strengths and weaknesses of the current version of the computational protocol will be explored, and a more efficient approach will be proposed. The development of more robust computational methods to predict amino-acid changes needed for activity is of the utmost importance as the need for experimentally probing randomized sequences would be greatly reduced, rendering the route to novel biocatalysts much more efficient. This might represent a cheap and environmentally friendly alternative for industries to produce active catalysts for any desired target.

Fields of science (EuroSciVoc)

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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.

Call for proposal

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FP7-PEOPLE-2013-CIG
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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.

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

UNIVERSITAT DE GIRONA
EU contribution
€ 100 000,00
Address
PLACA SANT DOMENEC 3
17004 Girona
Spain

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Region
Este Cataluña Girona
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

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