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Content archived on 2024-05-27

DNA Replication and Biomolecular Recognition

Objective

DNA replication is at the core of life and strongly appeals to the imagination. It is also a textbook example of template directed synthesis, involving enzyme-assisted molecular recognition of incoming bases by the template strand. Yet, in spite of much effort, many fundamental questions about its mechanism are open. In this research line, using a quantumchemical approach, we aim at two main objectives: (1) understanding the electronic nature of molecular recognition in DNA base pairs, in artificial mimics thereof and in larger, macromolecular aggregates of related systems; (2) unravelling the mechanism of the highly accurate, enzyme-assisted DNA replication and, in particular, understanding the role of hydrogen bonding, steric factors and solvent effects in this multistep process. The two subprojects are intimately connected and reinforce each other. We wish to explore the possibilities of rationally designing monomers whose capability to undergo self-organization can be switched on or off chemically (by a third agent) or physically (by radiation). Potential applications are the controlled and selective formation of macromolecules, nanostructures and materials. Furthermore, a better knowledge and so tuning and control of the DNA replication process is envisaged. On the long term, we hope to contribute to the development in general of quantumchemical approaches to biologically relevant problems, i.e. quantumbiology. Our computations are mostly based on density functional theory (DFT) but also on high-level ab initio theory as well as molecular mechanics (MM). Extensive validation studies, by others and us, have shown that DFT is the method of choice, both in terms of efficiency and accuracy, for large biochemically relevant molecules that involve hydrogen bonding. Our approach furthermore involves the application and further development of hybrid QM/MM techniques for tackling realistic model systems of the template–primer–enzyme complex involved in replication.

Fields of science (EuroSciVoc)

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Keywords

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Topic(s)

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Call for proposal

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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.

MC-ERG - European Re-integration Grants (ERG)

Coordinator

UNIVERSITAT DE GIRONA
EU contribution
€ 45 000,00
Address
PLACA SANT DOMENEC 3
17004 Girona
Spain

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Region
Este Cataluña Girona
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

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