Objective
In this multidisciplinary cooperation the methods of molecular modelling, structure determination and microbial techniques are applied to the analysis of protein stability, folding and functional properties, with the aim of understanding the underlying mechanism at the atomic level.
The research associated with this project utilizes prior work associated with the protein engineering of Barnase which has generated some 50 mutants all in relation to stability and activity.
The results which have been obtained to date can be divided into 3 categories:
development of research tools;
results aiming at the understanding of the mechanism of folding and stability;
results aiming at the understanding of the mechanism of enzyme kinetics.
Development of the research tool box:
In addition to various X-ray crystal structures which are already available for Barnase solution structure of Barnase has been determined by nuclear magnetic resonance (NMR).
Resultsaiming at the understanding of the mechanism of folding and stability:
The thermal stability of wild type Barnase (WT) and the T16S-mutant was investigating using high-sensitivity Differential Scanning Calorimetry (DSC).
Results aiming at the understanding of the mechanism of enzyme kinetics:
These include a study on the subsite specificity of the transesterification reaction catalysed by Barnase; modelling and analysis of the Barnase utilizing a pentanucleotide transition state model; the molecular dynamic simulation of barnase in the presence of 5 phosphate ions CH3OPO4 and the simulation of histidine protonation and deprotonation.
In the present project a multi-disciplinary approach is applied to the analysis of protein stability, folding and functional properties, with the aim of providing understanding at the atomic level of the underlying mechanisms.
It integrates experimental studies including site directed
mutagenesis, denaturation studies, analysis of catalytic parameters, as well as structural studies by x-ray diffraction and 2D NMR techniques, with theoretical analyses that combine molecular mechanics, and knowledge based modelling with dynamical simulations and free energy calculations. It will moreover be applied to a unique system, the enzyme barnase, and related microbial endonucleases which has proven to be a superior paradigm for such studies. This system can also be used to analyze protein-nucleic acid interactions and to experiment with design of G-binding peptides.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology materials engineering crystals
- natural sciences chemical sciences analytical chemistry calorimetry
- natural sciences chemical sciences catalysis
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
2611 XT Delft
Netherlands
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.