Projects / Programmes
Characterization of ligand-receptor interactions
| Code |
Science |
Field |
Subfield |
| 1.04.00 |
Natural sciences and mathematics |
Chemistry |
|
| Code |
Science |
Field |
| P351 |
Natural sciences and mathematics |
Structure chemistry |
non-covalent interactions, NMR spectroscopy, laser tweezers, screening, fragment-based design
Researchers (11)
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0104 |
National Institute of Chemistry |
Ljubljana |
5051592000 |
21,546 |
Abstract
Experimental methodology for investigation of ligand-receptor interactions based on high-resolution nuclear magnetic resonance (NMR) and molecular force spectroscopy will be implemented and developed. In particular generally appearing problems of large molecular weight of the protein target and low solubility of ligands in aqueous solution will be considered. Development of experimental methodology will be focused on determination of experimental parameters, which allow identification of ligand binding to protein targets and quantitative determination of non-covalent interactions in formation of ligand-receptor complexes. Precise identification of ligand binding is crucial for effective screening approaches. Knowledge of nature and energetics of non-covalent interactions between the ligand and receptor functional groups offers essential information for rational drug design and improvement of theoretical algorithms for investigation of drug-receptor complexes.
Significance for science
Results of project contribute to understanding of ligand-receptor interactions, which are ubiquitously essential in biological processes and have also important applications in biotechnology. The low energy level of biological processes is a consequence of non-covalent interactions between molecules. The nature and energetics of those non-covalent interactions are still poorly understood. The accurate assessment of ligand-receptor interactions contributes to development of structure prediction algorithms for modelling bio-molecular systems like ligand-receptor and enzyme-substrate complexes, which will improve the existent drug-design methodologies. The current drug-design algorithms are largely unsuccessful due to the approximations imposed by the simple "lock and key" model of drug action, which are not considering the conformational changes imposed by the interactions of receptor and ligand molecules. The detailed knowledge of ligand-receptor interactions is important for understanding the function and activity of variety of biological systems and can significantly contribute to the research in other fields, as are biology, medicine and pharmacy.
Significance for the country
Project is based on the collaboration of researchers from the institute, university and industry and is harmonized with the National Research and Development Project. New more efficient approaches for drug discovery can accelerate the development of new drugs against human diseases and can reduce the cost of development of new drugs. Therefore these approaches can be useful also for the Slovenian pharmaceutical industry. Implemented methodology is used for realization of actual industrial projects. Results are published in the world recognized top scientific journals and promote Slovenian science in the world. Young researchers (Ph. D students) are part of the research team and are able to gain general knowledge of high-resolution NMR spectroscopy, molecular modelling and the rational drug design methodologies. They gain important knowledge required for realization of basic research project as well as development project in pharmaceutical industry. They collaborate with researchers from university and industry and obtain various perspectives for their future employment.
Most important scientific results
Annual report
2008,
2009,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
