Projects / Programmes
Molekulske simulacije, bioinformatika in načrtovanje zdravilnih učinkovin (Slovene)
January 1, 2009
- December 31, 2013
| Code |
Science |
Field |
Subfield |
| 1.04.00 |
Natural sciences and mathematics |
Chemistry |
|
| Code |
Science |
Field |
| 1.04 |
Natural Sciences |
Chemical sciences |
Researchers (16)
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0104 |
National Institute of Chemistry |
Ljubljana |
5051592000 |
21,007 |
Significance for science
The research program is targeted at considerable improvements of our knowledge of enzyme catalysis, receptor activation mechanisms, and hydrogen bond dynamics. The key questions concerning enzymatic reactions are not yet properly understood and issues like the role of long-range electrostatic interactions, fluctuations and tunneling remain unclear. In particular, we clarified the relevance of hydrogen atom tunneling for biocatalysis; we also proposed the catalytic mechanism of the MAO B enzyme. From proper understanding of the rate limiting step one can devise the structure and charge distribution of the transition state that has potential application for rational drug design based on transition state analogs. In parallel we studied hydrogen bonded systems that are useful as model systems for enzyme centers with much smaller conformational space. Thus, the proposed project advanced the forefront of research in all these highly relevant fields and notably contributed to the development of science. New molecular targets and development of novel antibiotics directed at these targets are a challenge for a scientist in the field of biomedicine on one hand and on the other hand a pressing need of medicine for introduction of novel drugs into therapy because of unmet medical needs and fast development of bacterial resistance towards current antimicrobial drugs. The contribution to the development of science was also validation and characterization of DNA gyrase as molecular target for the development of novel antimicrobials and importance of this targets in pathology of various bacterial infections. The most important result is the discovery of novel antibiotics and enzyme inhibitors and knowledge about their mode of action. Also, important new knowledge will result from experimental determination of structure of the ligand–enzyme complex which will enable insight into underlying molecular mechanisms. The results of our work were published in highly ranked journals and presented at international conferences. We maintain active collaboration with Arieh Warshel, 2013 Chemistry Nobel Prize Laureate.
Significance for the country
Our studies give additional insight into structure, binding and reactivity of enzymes, which is a necessary condition for drug design. We are the only group in this country dealing with computational aspects of biocatalysis. We are the only group in Slovenia where tunneling in the systems of biological relevance is studied. No other group is offering comparable amounts of advanced computational support to vibrational spectroscopy, hence the active involvement of our group via the proposed project is of vital importance for the quality of science in Slovenia. This research program is of importance to broaden the knowledge, necessary for persistence and development of pharmacology. Development of pharmacology is crucial for parallel development of other disciplines in medicine, pharmacy, therapeutics and toxicology. Permanent development of pharmacology enables our equivalent participation and communication in the scientific and biomedical international community. For example neurotrophic factors and their receptors are crucial drug targets in the therapeutics of neurodegenerative diseases, pain, and cancer. Research in this field will help our group to find more scientific contacts with foreign scientists and international research funding. Regardless that we are doing mostly basic research, new contacts have been found with pharmaceutical industry and we already started developing new methods and techniques, which are basis for new drugs development and drug registration procedures. Results of the proposed research plan will widen the knowledge on drug action and to more rational drug use. Many of the results of the proposed research plan can lead to better pharmacotherapy or at least better knowledge and understanding of main and side effects of drugs, observed in clinical practice. When introducing new medicines to Slovenia, a good knowledge of pharmacology is crucial. The knowledge about basic mechanisms of drug action is helpful when introducing new drugs into pharmacotherapy. Some rare side effects can be more easily observed and reported. One of the national priorities is also to keep up and further develop research work at University level. Quality schools will enable good academic atmosphere, necessary for bringing up ambitious graduates, as well as educating future teachers of pharmacology and pharmacogenomics. The knowledge of pharmacology is essential for rational use of new, more and more expensive drugs in Slovenia and worldwide. Quality graduates with a broad knowledge of pharmacology are not needed just in biomedical sphere. They will find their place in pharmaceutical industry and in public administration dealing with complex procedures of drug registration and pharmacovigillance. The research activity directed towards development of a novel chemical entity to the end of preclinical research has been completed successfully in this laboratory for biological systems in which various enzymatic targets and chemical classes of inhibitor molecules were studied. There is also a continuously growing interest of the world pharmaceutical industry to promote an intense collaboration with innovative groups in academia. Such collaboration is the basis for formation of high-tech biotechnological companies what has been a priority for the Slovenian economic development of the 21st century. Functional knowledge obtained and developed by young researchers of the project team will be a foundation on which these high-tech biotechnological companies can be organized. The resulting products which can be commercialized are an important contribution towards the economic exploitation of existing infrastructure of academic research institutions. Novel knowledge obtained by this project will contribute to further development of the field of pharmacy, biotechnology and biomedicine in Slovenia. Affirmation of the national identity is reflected in publications in high ranked journal and patenting on the world scale.
Most important scientific results
Annual report
2009,
2010,
2011,
2012,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2009,
2010,
2011,
2012,
final report,
complete report on dLib.si
