Projects / Programmes source: ARIS

Molecular Simulations, Bioinformatics and Drug Design

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
P410  Natural sciences and mathematics  Theoretical chemistry, quantum chemistry 

Code Science Field
1.04  Natural Sciences  Chemical sciences 
3.01  Medical and Health Sciences  Basic medicine 
Multiscale simulation, quantum chemistry, QM/MM, enzymatic reactions, catalysis, molecular docking, monoaminergic system, biogenic amines, computer-added drug design, monoamine oxidases, topoisomerases, neurodegeneration, cancer, enzyme inhibition.
Evaluation (rules)
source: COBISS
Data for the last 5 years (citations for the last 10 years) on March 4, 2024; A3 for period 2018-2022
Data for ARIS tenders ( 04.04.2019 – Programme tender , archive )
Database Linked records Citations Pure citations Average pure citations
WoS  246  5,379  4,455  18.11 
Scopus  248  5,735  4,811  19.4 
Researchers (9)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  38252  PhD Kaja Bergant Loboda  Chemistry  Junior researcher  2019 - 2021  32 
2.  54668  Barbara Herlah  Pharmacy  Junior researcher  2020 - 2024  22 
3.  08611  PhD Janez Mavri  Chemistry  Head  2019 - 2024  367 
4.  50405  PhD Matic Pavlin  Chemical engineering  Researcher  2019  36 
5.  25493  PhD Andrej Perdih  Pharmacy  Researcher  2019 - 2024  263 
6.  50613  PhD Alja Prah  Chemistry  Researcher  2019 - 2022  22 
7.  56956  Martina Rajić  Chemistry  Junior researcher  2022 - 2024 
8.  20393  PhD Jernej Stare  Chemistry  Researcher  2019 - 2024  157 
9.  15708  PhD Neli Vintar  Chemistry  Researcher  2019 - 2024  149 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0104  National Institute of Chemistry  Ljubljana  5051592000  20,869 
The proposed work will include multiscale simulation of enzymatic reactions and advanced structure-based and simulation-driven drug development followed by the preclinical characterization of novel biologically active agents. Atomistic insight into the structure-function relationship of biological macromolecules is of central importance for understanding their function and for subsequent modulations of its function by various ligands.   Our research will be based on the state-of the-art methods of biomolecular simulation, in particular multiscale treatment of enzymatic reactions, to get insight into the nature of enzyme catalysis as well as reactions in solution. We will address the fundamental open issue in enzymology, namely what is the source of the catalytic function of enzymes. Subsequently, advanced methods of computer-aided molecular design that couple biomolecular simulations with static design approaches will also be applied to identify novel biologically interesting compounds. We will focus our studies on two systems: monoaminergic system in the central nervous system, and DNA topology-changing molecular motors such as human type II topoisomerases, crucial targets in anticancer therapy.   One set of systems will include flavoenzymes, mainly monoamine oxidases (MAO) A and B, monoamines and receptors. MAO enzymes metabolize biogenic amines such as dopamine and serotonin. Irreversible inhibition of MAO has neuroprotective effect since metabolites of dopamine and other biogenic amines are to certain extent neurotoxic. We will simulate the rates of MAO catalyzed reactions and its irreversible inhibition. One of the goals is to provide additional information for the development of novel drugs to treat neuropsychiatric diseases. The other system, the human DNA topoisomerase IIα, represents an attractive and established target for the development of novel anticancer drugs. These complex molecular motors capable of changing the topology of the DNA molecule are well conserved and abundant enzymes and their biological role is to preserve the genome integrity and enable cell replication. The principal goal of the proposed research here will be to provide additional understanding to its function through computational and preclinical evaluation methods to discover novel catalytic inhibitors of topo IIα, taking advantage of an alternative inhibition paradigm not yet exploited in cancer therapy.
Significance for science
The combined use of molecular simulation methods and experimental studies 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 a key element for the understanding, prevention and treatment of neuropsychiatric diseases. With the knowledge of the chemical mechanism of the metabolism of biogenic amines and irreversible inhibition of the enzymes involved in the process it is possible to design novel drugs. New molecular targets and development of novel drugs directed at these targets represents a challenge for molecular medicine.   The growing number of cancer patients worldwide presents a pressing need in human medicine for the introduction of novel drugs into therapy. Our contribution to the forefront of research in this compelling field will be the study of topoisomerase II? inhibitors for the development of anticancer drugs by exploiting an alternative inhibition mechanism to circumvent some of the known limitations of topo II poisons used in therapy. In particular, new knowledge of general interest will result from the experimental determination of the structure of the ligand–enzyme complexes which will enable insights into underlying molecular mechanisms. In addition, our research will enhance mechanistic understanding of the monoaminergic system and development of novel topoisomerase II? inhibitors as potential anticancer compounds.   In addition to medicinal sciences, the foreseen impact of our research provides valuable improvements in the field of enzymology. Elucidation of the source of catalytic performance of enzymes is of great interest in biochemistry, chemical physics, pharmaceutical science and biology. Our expertise in chemical reactivity, hydrogen bonding and solid state chemistry provides additional benefits for the development of science in the aforementioned disciplines.
Significance for the country
The research activity directed towards development of novel drugs and the molecular understanding of the monoaminergic system, provides solid knowledge applicable to the Slovenian pharmaceutical industry, clinical practice and education process. The members of our research group are involved in teaching at Faculties of Pharmacy and Medicine at the University of Ljubljana and transfer their knowledge to students. Knowledge is also transferred to high school students, with noticeable success of their research projects at international competitions. The majority of doctoral students from our laboratory are later employed by the pharmaceutical industry, hence their functional skills acquired within our group have been regularly transferred to the fields outside academia. Two doctoral students from the group have received the prestigious Krka award for their doctoral thesis in the last four years. There is also a continuously growing interest of the international pharmaceutical industry to promote an intense collaboration with innovative groups in academia. Such collaboration can potentially evolve in the formation of high-tech biotechnological companies, which has been declared as a priority for the Slovenian economic development. Deliverables of our research with potential for commercialization, mainly novel drug candidates, are an important contribution towards the economic exploitation of existing infrastructure of academic research institutions. Indirectly, the proposed research program will influence the national identity as a consequence of the publication of scientific achievements in reputed international journals and patents. Hopefully, the efforts of our research team will result in developing original chemical entities (or at least give direction for their synthesis) that will be able to enter preclinical testing.
Most important scientific results Interim report
Most important socioeconomically and culturally relevant results Interim report
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