Compounds of the polyphenol family, and more particularly of the anthocyanin family, are produced within plants through enzymatic cascades. They are important for plants because their nature can modify the color of these, and in the general context of climate change make them more resistant to UV. Within this enzymatic cascade, the enzyme DFR (dihydroflavonol 4-reductase) plays a key role.

The DFR enzyme catalyzes the reduction of dihydroflavonols into leucoanthocyanidins. DFRs from different plant organisms showed substrate specificities apparently related to subtle amino acid sequence mutations. Many studies have been conducted on this type of enzyme, but there is not yet a systematic understanding of how this specificity is determined at the molecular level. This project aims to elucidate the basis of the specificity of the DFR enzyme and its structure-function relationship.

This work will require a wide spectrum of theoretical approaches: homology reconstruction method, docking methods, molecular dynamics simulations, quantum chemistry calculations and possibly QM/MM type simulations. The possible consideration of the influence of the protein environment may require the use of protein/protein docking method. Exchanges with our collaborators (T. U. Wien, Austria) will be preponderant in the choice of approaches to be applied.

Mots clés. Molecular Modeling, theoretical Chemistry; Enzymatic specifity; Polyphénols

Informations. This thesis funding has already been acquired, within the framework of the Franco-Austrian ANR PRCi DFR-SPEC (Substrate specificity of dihydroflavonol 4-reductase (DFR) – Let's complete the puzzle). The net monthly salary will rise from ≈1650€ in 2023 to ≈1850€ in 2026.

The work will take place at the Institut de Chimie de Nice-UMR CNRS 7272, Université Côte d'Azur and will be supervised by Pr. Serge Antonczak

The work will be carried out in close collaboration with our Austrian partners (Dr. C. Haselmair-Gosch- Pr H. Halbwirth, Technische Universität Wien, Institute of Chemical, Environmental and Bioscience Engineering).

The calculations will be carried out on the workstations owned by the team but also on university, regional and national calculation servers.

Ideally, the start of the thesis should take place on September 1 or October 1, 2023.

How to apply. The candidate holding a master's degree (or equivalent diploma), must demonstrate solid knowledge in Molecular Modeling / Theoretical Chemistry. A good level of English is essential in order to interact with Austrian collaborators and to be able to write all communications (publications, scientific journals, posters) during the thesis.

The candidate must provide a cover letter, a curriculum vitae and 2 letters of recommendation to the address: Serge.Antonczak@univ-cotedazur.fr

Application deadline: June 15, 2023