Objective
The interaction between aromatic ligands (e.g. daunomycin) and deoxyribonucleic acid (DNA) has been the object of considerable research in connection with the use of such molecules as anti-cancer drugs. Drug design usually aims to exploit the specificity of gene sequence in the cell DNA, since diseases are often connected with gene defects.
The action of the ligand (i.e. drug) has been interpreted as an intercalation into the DNA structure with some unknown binding mechanism lengthening the helix. To the best of our knowledge a microscopic interpretation of the mechanism and rate based on the dynamics of the ligand-DNA interactions is still lacking. We thus propose a complete theoretical investigation of the mechanism of the intercalation which considers the effects of the molecular nature of the drug and of the portion of DNA exposed to the ligand action.
The goal of this research is to provide a molecular understanding of and a predictive theory for rational improvement of drug design. In addition to the value of the project in the biomedical field and therefore in the development of European research concerning anti-cancer drugs, an advanced training in multi-disciplinary subjects will be necessarily provided to the fellow in her chosen field of future research. Intercalation is in fact a complex process involving the motion of the ligand and the local DNA structure (which must change to accommodate the drug) and rearrangement of surrounding solvent and ion molecules.
A multi-dimensional free energy surface, constructed via electronic structure calculations and Molecular Dynamics computer simulations, and a generalized Langevin description approach will be employed to analyze the dynamics of the motion leading to the binding and to construct an explicit theory for the intercalation rate constant. Particular attention will be paid to the key drug-DNA interactions involved and to the influence of changing the base sequence, critical factors for the intercalation.
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 medicinal chemistry
- natural sciences biological sciences genetics DNA
- natural sciences mathematics applied mathematics mathematical model
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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.
FP6-2005-MOBILITY-5
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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
PARIS
France
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.