Objective
Kinase proteins are key to signaling in eukaryotic cells, so it is not surprising that their dysfunction has been implicated in human diseases such as cancer and inflammatory disorders. As a result, kinases have become important targets for drug discovery. The majority of kinase inhibitors bind to the ATP-binding site, which is highly conserved among the different kinases. In order to increase inhibitor selectivity toward a desired target kinase, the focus has turned to developing inhibitors which bind to inactive conformations or allosteric sites.
The techniques frequently used to study inhibitor binding such as X-ray crystallography and docking are limited because they only sample a single structure. In reality, a protein is characterized by an ensemble of structures. Free energy calculations can sample many different conformations and provide a clear picture of the mechanisms of inhibitor binding. Since straightforward molecular dynamics simulations suffer from a time scale problem we use a novel computational technique, metadynamics, to enhance sampling. Using metadynamics calculations we propose to investigate the binding mechanisms of inhibitors which target the inactive conformation and allosteric sites.
We focus on two proteins which are targets for cancer therapy: p38 mitogen-activated protein kinase and Abl.
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.
- medical and health sciences basic medicine pharmacology and pharmacy drug discovery
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
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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.
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
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2011-IEF
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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
WC1E 6BT LONDON
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.