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Content archived on 2024-05-27

Solvent dynamics in enzymatic catalysis: a molecular dynamics simulations and kinetic terahertz absorption spectroscopy study

Objective

With ever new emerging experimental techniques and advances in computer simulations, it could be shown that solvation dynamics plays a fundamental role in many processes that are essential to life on a molecular scale. In particular, an ongoing intensive activity aims to elucidate the dynamical features of hydration water in the picoseconds time scale and terahertz (THz) spectral range, owing to the fact that numerous processes in water occur on this time scale.
The main aim of the project MOLDYKITA is to characterize the solvation dynamics at THz frequencies for a physiologic scenario of enzymatic catalysis, i.e. the interaction between a zinc metalloprotease enzyme and collagen-like molecules. The study will be carried out by means of molecular dynamics (MD) simulations and time resolved kinetic THz absorption spectroscopy (KITA) techniques, thus providing a robust basis for the interpretation of the experimental results.
The catalytic domain of human membrane type-1 matrix metalloproteinase (MMP) will be used as model enzyme. Two collagen-like molecules, a highly flexible single chain peptide (SCP) versus a more rigid triple helical peptides (THP), will be used as model substrates and compared in the process of substrate-enzyme docking.
This project will provide a microscopic picture of the changes in the water motions associated with substrate binding in the MMP-SCP and MMP-THP system. The aim is to answer to fundamental questions regarding solvation in enzyme catalysis, e.g. do water networks motions play a role in enzymatic catalysis and can water networks sense different substrates. The results of the project will show whether changes in protein and solvent dynamics are not mere epiphenomena, but have a vital role in substrate binding and recognition. These answers are of paramount importance for the fields of Physics, Chemistry and Biology and might turn out to be crucial for technological applications in drug design.

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2012-IEF
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Funding Scheme

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MC-IEF - Intra-European Fellowships (IEF)

Coordinator

RUHR-UNIVERSITAET BOCHUM
EU contribution
€ 161 968,80
Address
UNIVERSITAETSSTRASSE 150
44801 Bochum
Germany

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Region
Nordrhein-Westfalen Arnsberg Bochum, Kreisfreie Stadt
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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