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Projects / Programmes source: ARIS

Molecular Simulations, Bioinformatics and Drug Design

Periods
Research activity

Code Science Field Subfield
1.04.00  Natural sciences and mathematics  Chemistry   
1.09.00  Natural sciences and mathematics  Pharmacy   

Code Science Field
B120  Biomedical sciences  Molecular biophysics 

Code Science Field
1.04  Natural Sciences  Chemical sciences 
3.01  Medical and Health Sciences  Basic medicine 
Evaluation (rules)
source: COBISS
Researchers (12)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  37778  Deni Bačič    Technical associate  2015 - 2017 
2.  38252  PhD Kaja Bergant Loboda  Chemistry  Junior researcher  2015 - 2018  32 
3.  29677  PhD Matjaž Brvar  Pharmacy  Researcher  2014  55 
4.  08611  PhD Janez Mavri  Chemistry  Head  2014 - 2018  367 
5.  50405  PhD Matic Pavlin  Chemical engineering  Researcher  2018  36 
6.  25493  PhD Andrej Perdih  Pharmacy  Researcher  2014 - 2018  263 
7.  27837  PhD Gordana Pirc  Chemistry  Researcher  2014  17 
8.  33211  PhD Barbara Pogorelčnik  Materials science and technology  Researcher  2014 - 2015  26 
9.  50613  PhD Alja Prah  Chemistry  Junior researcher  2017 - 2018  22 
10.  33210  PhD Matej Repič  Pharmacy  Researcher  2014 - 2015  26 
11.  20393  PhD Jernej Stare  Chemistry  Researcher  2014 - 2018  157 
12.  15708  PhD Neli Vintar  Chemistry  Researcher  2018  149 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0104  National Institute of Chemistry  Ljubljana  5051592000  20,878 
Abstract
Our work will be directed towards chemical damages of proteins and DNA that represent inital steps of neurodegenerationa and carcinogenesis. We will proceed with flavoenzymes, a group of enzymes responsible for neurodegeneration and DNA topoisomerases, a group of enzymes that represent a target for treatment of neoplasia and antimicrobial therapy. Our research will be based on state-of' the-art methods of biomolecular simulation, for instance QM/MM simulation of enzyme reactions and related methods for the first principle characterization of biological systems. In part related to quantization of nuclear motion we will also develop our own computational methodology. Our planned studies include flavoenzymes, to large extent we will study monoamine oxidase B (MAO B), an enzyme that metabolizes dopamine and MAO A, an enzyme that metabolizes serotonin. Ireversible inhibiltion of MAO has neuroprotective effect since metablites of dopamine and other biogenic amines are to certain extent neurotoxic. MAO mechanims are relevant for development of novel drugs used for treatment of Parkinson disease and for prevention of neurodegeneration. DNA topoisomerases represent an attractive and validated target for development of novel antimicrobial and anticancer drugs. DNA topoisomerases are well conserved and abundant enzymes and their biological role is preservation of genome integrity. The principal goal of proposed research is design, biophysical characterisation and biological testing of novel DNA gyrase inhibitors as antimicrobials and inhibitors of DNA topisomerase IIA as anticancer drugs.
Significance for science
Application of combination of molecular simulation methods with experiment in the field of drug development is an emerging topic of molecular medicine. Structural and mechanistic understanding of the target is a prerequisite for successful de novo design of drug candidates. We developed expertise in the field of flavoenzymes that represent key element for understanding, prevention and treatment of neurodegenerative diseases and depresion. With the knowledge about chemical mechanism of biogenic amines metabolism and irreversible enzyme inhibition it is possible to design novel drugs. New molecular targets and development of novel drugs directed at these targets are a challenge for a scientist in the field of biomedicine. Fast development of bacterial resistance towards current antimicrobial drugs on one hand and growing number of cancer patients worldwide presents a pressing need in human medicine for introduction of novel drugs into therapy. The contribution to the development of science will be the study of DNA gyrase as a molecular target in pathology of various bacterial infections for the development of novel antimicrobials and topoisomerase IIa for the development of anticancer drugs. In particular, new knowledge of general interest will result from experimental determination of structure of the ligand–enzyme complexes which will enable insights into underlying molecular mechanisms. The most important result will be the discovery of DNA gyrase inhibitors as novel antibiotics and inhibitors of the human enzyme topoisomerase IIa as potential anticancer compounds and knowledge about their mode of action.
Significance for the country
The research activity directed towards development of a novel chemical entities to the end of preclinical research has been completed successfully in this laboratory for a variety of biological systems in which enzymatic targets and rational design of inhibitor molecules of diversified chemical classes were performed. Members of the laboratory are involved in teaching at Faculties of Pharmacy and Medicine at University of Ljubljana and transfer their knowledge to students. The majority of doctoral students from our laboratory are later employed by industry. Two doctoral students from the group have received Krka price for their doctoral thesis in the last four years. 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 potentially a 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. Indirectly, the programme will influence the national identity as a consequence of publication of scientific achievements in international journals and patents. Furthermore, the efforts of the research team to develop an original chemical entity into drug will contribute to the international distinction of our research
Most important scientific results Annual report 2014, 2015, final report
Most important socioeconomically and culturally relevant results Annual report 2014, 2015, final report
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