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Understanding the molecular mechanism of enzymatic processes by a combination of NMR spectroscopy and molecular dynamics simulations

Objectif

"Essentially all the biochemical processes taking place in living organisms require the intervention of enzymes, which are proteins capable of increasing the rates of chemical reactions by up to 15 orders of magnitude. A detailed definition of the molecular basis of the action of enzymes will not only represent a key advance in our understanding of the fundamental principles of macromolecular behavior, but also provide new opportunities for the rational development of effective treatments for human disease, and for the control of chemical processes in biotechnology. In this application, we propose to characterize in detail the enzymatic processes of two important proteins, cyclophilin A and PagP, by using an interdisciplinary approach in which experimental measurements are incorporated as structural restraints in molecular dynamics simulations. The innovative aspect of this project is the use of chemical shifts, which are the parameters that can be measured most readily and accurately in nuclear magnetic resonance spectroscopy, for protein structure determination. This approach, which has been pioneered in the host lab, enables to determine with high accuracy the structures of proteins in states that are not easily accessible through other types of measurements. We will therefore have the opportunity to gain access to conformations that are invisible by standard methods of structural biology, and in this way to clarify the mechanism of action of two important enzymes."

Champ scientifique (EuroSciVoc)

Programme(s)

Thème(s)

Appel à propositions

FP7-PEOPLE-2010-IEF
Voir d’autres projets de cet appel

Régime de financement

MC-IEF - Intra-European Fellowships (IEF)

Coordinateur

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Contribution de l’UE
€ 200 049,60
Adresse
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
Royaume-Uni
Région
East of England East Anglia Cambridgeshire CC
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
Aucune donnée