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Fast yet accurate routine rational design of novel enzymes

Project description

Designing enzymes for sustainable industries

Enzymes are usually proteins that act as catalysts to speed up chemical reactions in living organisms. They play a critical role in many cellular processes, including DNA replication and protein synthesis, and have also been exploited in industry owing to their beneficial characteristics. However, current methods for designing enzymes for industrially relevant targets are slow and expensive. The goal of the ERC-funded FASTEN project is to develop a new computational approach to designing efficient enzymes quickly and accurately for industrial applications. Researchers will employ tools based on machine learning, correlation and coevolution, as well as computational geometry to predict mutations that enhance enzyme activity. Insight into the catalytic efficiency of these new enzymes will help improve the design protocol and contribute to sustainable industrial processes.

Objective

Life could not be sustained without the presence of enzymes, which are responsible for accelerating the chemical reactions in a biologically compatible timescale. Enzymes present other advantageous features such as high specificity and selectivity, plus they operate under very mild biological conditions. Inspired by these extraordinary characteristics, many scientists wondered about the possibility of designing new enzymes for industrially-relevant targets. Unfortunately, none of the current enzyme design strategies is able to rapidly design tailor-made enzymes at a reduced cost. This is limiting the general routine application of enzyme catalysis in industry, and thus the chemical manufacturing competitiveness. The goal of this project is to develop a fast yet accurate computational enzyme design approach for allowing the routine design of highly efficient enzymes. FASTEN combines computational chemistry, deep learning, graph theory, and computational geometry for controlling the complexity of enzyme catalysis in a new computational protocol that will capture the chemical steps and conformational changes that take place along the catalytic itinerary. Active site and distal activity-enhancing mutations are predicted based on correlation and co-evolutionary-based guidelines, and the catalytic potential of the new designs is estimated by means of geometry-based oracles. This new computational approach will be validated with the design of enzymes presenting complex conformational dynamics and multi-step mechanisms. The experimental evaluation of many of the designs will finally reveal the potential of this new approach for the fast routinely design of industrially-relevant enzymes. FASTEN has the potential of making the routine design of enzymes possible, thus improving our current lives and leading to a more sustainable world for our generations.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2022-COG

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Host institution

UNIVERSITAT DE GIRONA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 996 250,00
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.

€ 1 996 250,00

Beneficiaries (1)

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