Insight into the function of post-translational modifications of proteins via large-size scale and long-scale molecular dynamic simulations
The goal of the proposed project is to investigate the post-translational modifications (PTMs) of proteins. The result of this research will enable the investigations of the protein-based biological phenomena that almost always have PTMs involved (such as regulation of enzyme activities, and modifying protein stability). PTMs are complex and fundamental mechanisms of cellular regulation and have been associated with almost all known cellular pathways and disease processes. PTMs consist of a covalent modification of amino acids side-chains or the protein's C- or N-termini and therefore change their properties and dynamics. Moreover, depending on the biological purpose of a particular modification, PTM may or may not be reversible. PTMs occur after the synthesis of protein and may involve enzymes or occur spontaneously. PTMs have a vital role in almost all biological processes and numerous molecular functions. Therefore, the footprints of disruption in PTMs can be seen in many diseases, for instance, neurodegenerative disease (Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease), heart failure, autoimmune diseases, and cancer. There are more than 400 types of PTMs. Some of the PTMs seem very specific and to this moment can be found only in several types of proteins, like polyglycination, polyglutamylation, and tyronisation/detyronisation (abundant in the C-tail of tubulin). Detailed analysis and characterization of PTMs using experimental methods present significant challenges, mostly because of the labile transient nature of many of these modifications. Although there have been considerable advances in PTMs research made in the last decades, both experimental and theoretical approaches still experience difficulties in effectively analyzing their structural and dynamic effects on protein function and molecular mechanism. This project is aimed at addressing the question: How PTMs influence proteins' structure and function? Hence, the new interatcion sites for PTMs will be added UNRES coarse-grained force field that will enable the novel investigations in a crucial area of PMTs.
Details
- Financial Program Name:
- SONATA
- Organization:
- Narodowe Centrum Nauki (NCN) (National Science Centre)
- Agreement:
- UMO-2023/51/D/ST4/02288 z dnia 2024-07-24
- Realisation period:
- unknown - unknown
- Project manager:
- mgr Paweł Płaszcz
- Realised in:
- Dział Administracji
- Request type:
- National Research Programmes
- Domestic:
- Domestic project
- Verified by:
- Gdańsk University of Technology
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