Objective
Ras genes code for small GTPases that act as GDP/GTP-regulated molecular switches. This exchange induces a conformational change that allows them to interact with their downstream effectors, and thus participate as central control elements in signal transduction. Mutated forms of the Ras oncoprotein are found in more than 30% of all human cancers, justifying the extensive research on them. Ras effectors have convergently developed a common subdomain in their unrelated overall structure for their interaction with Ras. Although detailed knowledge about the thermodynamics and dynamics of the interaction with Ras has accumulated, the molecular mechanism at atomic detail of effector activation and thus specificity is still elusive. Crystallographic, NMR, and other spectroscopic studies show that the flexibility of their so-called “switch regions” majorly contributes to the adaptability of the Ras proteins to their various partners, including disorder-to-order transitions upon binding to their partners, and “structural polymorphism” in their different complexes and in the unbound forms. This incorporates another degree of difficulty on the understanding of the Ras:effector association. Although some studies have been previously carried out in order to rationalize the specificity of the Ras proteins towards their different effectors, they have been based only in the availability of Ras:effector crystal structures and taking a rather static point of view. In this work we intend to extend this to a large-scale bioinformatics and computational study, including driven-docking of Ras proteins and their effectors for which no complex structure is available but biological data supports complex formation. In a further step, Molecular Dynamics simulations both on the unbound partners and on their complexes will yield information accounting both for the binding affinity and for the intrinsic plasticity crucial in the recognition and regulation of Ras pathways
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- engineering and technology materials engineering crystals
- natural sciences physical sciences thermodynamics
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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-2007-2-2-ERG
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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
28029 Madrid
Spain
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.