Objective
The phosphate chemistry of nucleoside triphosphates (NTPs) is at the heart of crucial biological processes including the cell’s energy storage, signalling and copying genetic information. Computational modelling valuably expands the spatiotemporal resolution of experimental structural biology, providing a key contribution to the synergistic understanding of such complex processes.
However, our preliminary results on phosphatase reactions shed light on the qualitative inaccuracy of the state-of-the-art methodology capable of free energy bio-simulations.
Thus, the candidate will be trained to extend the host’s uniquely accurate and efficient electronic structure approaches to the scale of enzyme simulations, producing thermodynamic properties comparable to experiments. The candidate brings complementary computational biochemistry experience and reaction mechanistic knowledge to this collaboration, demonstrated in his successful computational-experimental phosphate catalytic enzyme studies. Our concerted developments will combine methods from the forefront of quantum chemistry, high-performance computing, rare event molecular dynamics, and biochemical modelling into a widely applicable open-access protocol, with a predictive power currently limited to main-group homogeneous catalysis modelling.
The reliability of the reaction mechanisms predicted by the developed method will be validated against kinetic experiments on wild-type and mutant Ras GTPases, connected to ca. one third of the cancer cell lines. Then, we will utilise the established protocol to understand the (regular and faulty) binding and incorporation of deoxy-NTPs and nucleoside analogue drugs during mitochondrial DNA polymerisation to a yet unknown atomistic detail. These results will provide a foundation for a comprehensive kinetic model for DNA polymerase fidelity and for the future rational optimisation of more selective and less toxic antiretrovirals.
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.
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine oncology
- natural sciences chemical sciences catalysis
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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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.
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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.
(opens in new window) HORIZON-MSCA-2024-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
1111 BUDAPEST
Hungary
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.