Genes or environment: How the protein surroundings affects their function (GENEN)

Main funder

Funder's project number: 332743

Funds granted by main funder (€)

  • 319 600,00

Funding program

Project timetable

Project start date: 01/09/2020

Project end date: 31/08/2024


To improve an enzyme or to design a new one, a detailed understanding of the underlying catalytic reaction mechanism is required. While serial femtosecond crystallography (SFX) has now opened up a new experimental window into the regime of into enzyme dynamics at the relevant time and spacial resolutions, the technique itself is limited to crystalline samples. Because crystal packing and/or other factors for crystallisation conditions can affect the conformational flexibility of the enzyme, it is unclear whether the mechanisms observed in SFX are the same, or even relevant for enzymes in solution. To address this challenge, we propose to combine time-resolved spectroscopy methods that span the wide range of time-scales involved in enzyme catalysis, on the one hand, and atomistic computer simulations on the other hand, to systematically investigate the differences between enzyme activity in solution and in crystals. Differences between reaction rates and spectral signatures of intermediates will be rationalised with molecular dynamics simulations to ultimately train a computational model with which the effects of crystal packing on enzyme catalysis can be predicted and results from SFX extrapolated from crystals to solution.

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Last updated on 2022-06-07 at 12:43