Projects / Programmes source: ARIS

Mathematical and simulation methods in studies of molecular structure and dynamics and non-equilibrium statistical mechanics

Research activity

Code Science Field Subfield
1.07.00  Natural sciences and mathematics  Computer intensive methods and applications   
1.02.00  Natural sciences and mathematics  Physics   

Code Science Field
B120  Biomedical sciences  Molecular biophysics 

Code Science Field
1.01  Natural Sciences  Mathematics 
Computer simulations parallelization of computer clusters speedup atomistic and mesoscopic scale computational fluid dynamics non-equilibrium statistical physics analytical solutions protein-ligand interactions anticancer drug design potential tumourgenicity of microwave radiation
Evaluation (rules)
source: COBISS
Researchers (16)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  31147  PhD Staš Bevc  Computer intensive methods and applications  Researcher  2015 - 2016  21 
2.  29677  PhD Matjaž Brvar  Pharmacy  Researcher  2015 - 2016  55 
3.  50430  Nika Eržen    Technical associate  2018  12 
4.  29487  PhD Aljaž Godec  Physics  Researcher  2015 - 2017  80 
5.  02287  PhD Milan Hodošček  Chemistry  Researcher  2015 - 2019  279 
6.  25435  PhD Janez Konc  Computer intensive methods and applications  Researcher  2015 - 2019  228 
7.  39116  Matija Kuclar  Neurobiology  Junior researcher  2016 - 2018 
8.  37452  PhD Samo Lešnik  Pharmacy  Researcher  2015 - 2018  57 
9.  34598  Mitja Ogrizek  Computer intensive methods and applications  Technical associate  2015  18 
10.  52000  Petra Papež  Computer intensive methods and applications  Junior researcher  2018 - 2019 
11.  36416  PhD Aleksandar Popadić  Computer intensive methods and applications  Researcher  2015 - 2019  20 
12.  19037  PhD Matej Praprotnik  Computer intensive methods and applications  Head  2015 - 2019  317 
13.  35381  PhD Jurij Sablić  Computer intensive methods and applications  Researcher  2015 - 2019  29 
14.  53609  Ema Slejko  Computer intensive methods and applications  Junior researcher  2019 
15.  01661  PhD Tomaž Šolmajer  Chemistry  Retired researcher  2015 - 2019  380 
16.  34530  PhD Julija Zavadlav  Physics  Researcher  2015 - 2016  37 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0104  National Institute of Chemistry  Ljubljana  5051592000  21,015 
Computer simulations have become indispensible in the research fields of molecular chemistry, structural biology, study of structure and dynamics of solutions etc. To be able to quantitavely describe larger and increasingly complex molecular systems we shall develop novel approaches which would enable longer simulations of larger molecular systems. This will significantly increase the effectiveness of studying structural dynamic and thermodynamic properties of macromolecular systems, soft matter and molecular solvents. Our solutions in particular with use of parallelization in computer clusters which have advanced to the tool of choice for the simulations of molecular systems will also contribute to increasing the computational efficiency and/or accuracy. The challenges of non-equilibrium statistical physics will be dealt with analytical studies of systems in non-equilibrium. In the area of applications we shall study the interactions between protein receptors and their ligands, potential tumourgenicity of microwave radiation and design novel chemical entities in the anticancer therapeutic field. The hybrid AdResS method which couples the atomistic and mesoscopic scales of a molecular system will be used for application to macromolecules, where we will model different macromolecular parts in various levels of detail. We will apply our multiscale solvents to study complex biomolecular systems such as lipid bilayers and to study ligand binding to an enzyme where only the active site and surrounding solvent are treated in full atomic detail. Due to the simulation speedup, which is enabled by our new multiscale approach, we will be able to study these complex systems without loss of accuracy using our Linux cluster. The computational fluid dynamics (CFD), which describes fluid dynamics using the Navier-Stokes equation, allows to model fluid flow on much larger/longer length and time scales. Our method facilitates the insertion of complex molecules into the atomistic domain via coarsegrained region and thus enables simulations in grandcanonical ensemble and under nonequilibrium conditions. A theoretical description of non-equilibrium microscopic systems is only possible on the level of probability theory and statistical physics. When dealing with such systems we lack 'universal' mathematical tools and paradigms as well as generic optimization principles. The present program will be focused on the development of mathematical-statistical methods with a goal to study selected fundamental open issues of statistical physics, from general theory and computational methods to applications. The analytical part will be directed towards developing methods to study functionals of single trajectories out of equilibrium or in non-equilibrium steady states. The developed formalisms will be applied to selected problems in the field of condensed matter theory, biophysics, biology and (bio)chemistry, pharmaceutical and materials science.
Significance for science
The effective simulation of biomolecular systems is largely hampered by the disparity of length and time scales involved in these systems. Nowadays, simulations of such systems are mostly carried out in separate scales using simulation approaches such as molecular dynamics. Significant advances in computer hardware have provided unprecedented physical insight in the dynamics of biomolecular systems. However, advances in computer hardware alone are not sufficient to reach the experimental length and time scales in these systems. Therefore, it is essential to develop multiscale methods that can resolve the wide range of length and time scales associated with the dynamics of biomolecular systems. Of particular interest is the coupling of these models and algorithms. This coupling is the subject of intense research efforts by several groups around the world and is considered as one of the most important areas for the advancement of computational physics and chemistry. Within the scope of the programme we will develop several multiscale models of water and salt solutions, as the most important solvents in biomolecular systems, that will speed up biomolecular simulations up to an order of magnitude. Our multiscale approaches will bridge the hydrodynamics from the atomic to macroscopic scale and enable the study of biophysical phenomena that are beyond the scope of either atomistic, mesoscopic, or macroscopic simulations. A theoretical description of fluctuations in non-equilibrium dynamics is a big and important scientific challenge world-wide. While the critical importance of fluctuation out of equilibrium is meanwhile well recognized, the field is sill in its infancy phase and thus relatively unexplored. Breakthroughs in the field are typically published in the elite physical journals (e.g. Phys. Rev. Lett.) as well as general scientific magazines (Nature, Science, PNAS, etc.). Of highest importance is the understanding of the relationship between the details of micro- and/or meso-scopic dynamics, inter-particle interactions and the statistics of functionals over trajectories, which might lead to numerous breakthroughs in the understanding of non-equilibrium phenomena in various fields. The research field is strongly interdisciplinary and spans over theoretical and mathematical physics all the way to theoretical physical (bio)chemistry. The highest relevance and timeliness of the proposed research is also reflected in the tight and intense collaboration of the members of the research program with leading scientist across Europe and world wide. The vivid cross-fertilization and entanglement of ideas and disciplines will enable further breakthroughs and advances in basic science in the future. The development of algorithms for binding sites detection on protein structures could provide new insights into the mode of action of these molecular machines and is fundamental to our understanding of the processes that govern binding of small ligands and biomolecules such as proteins or nucleic acids. The result of the proposed research program will be new tools for pharmaceutical modeling, free to researchers worldwide, available from our web server ProBiS (Protein Binding Sites) at http://probis.cmm.ki.si, distinguished for its comprehensible graphical interface. The developed tools will enable researchers to predict binding of molecules to proteins, and to evaluate their binding affinity using molecular modeling methods. We expect new insights into the binding of ligands to proteins. Developed tools will be used to resolve outstanding issues in pharmacy, for example, in the development of antimicrobial agents. New molecular targets and development of novel drugs directed at these targets are a challenge for scientists in the field of biomedicine. 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 b
Significance for the country
The successful work of our program group gives the opportunity to perform excellent research and  transfer our knowledge and experience to other users, both from the research community and industry. We also participate in the educational process, by mentoring diploma and doctoral students, and collaborate with users to solve their given problems. Functional knowledge obtained and developed by the programme team will be a foundation on which in perspective 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.  Within the programme we will develop and carry out multiscale simulations of biomolecular systems combining various numerical approaches. e.g., all-atom and coarse-grained molecular dynamics methods as well as computational fluid dynamics techniques. The developed methods we also employ in the pedagogical environment and use for popularization of the scientific field. The programme group members have been mentors/comentors for several doctoral thesis in physics, computer science, pharmaceutical science, and chemistry. The project group members are also lecturers at the Faculty of Mathematics and Physics, University of Ljubljana. The multiscale methods, which we will develop and employed in this programme, should pave the way for simulation based studies of pharmaceutical and medical interest, e.g., targeted drug delivery. Since the programme group members collaborate with the Slovenian pharmaceutical industry, i.e., Lek (Sandoz) and Krka, we envisage that our biomolecular simulation results may be of interest for potential applications in the pharmaceutical industry. The advance of basic science is one of the most important driving forces of the development of modern society. Namely, basic science enables and facilitates the proliferation of applied science and thus eventually also fuels the technological advance and economic growth. Elucidation of general principles of non-equilibrium dynamics can therefore also significantly contribute to fields outside the realm of physics. A timely and effective implementation of the evolution and growth of inter- and multi-disciplinary basic research is one of the leading trends of modern science. It is therefore vital that Slovenia keeps up with the leading European and worldwide scientific trends. The proposed research will also importantly contribute to top-quality education of young researchers and other aspiring young scientists (graduate and postgraduate students). An important integral part of the program are close international collaborations with leading scientific institutions. The program is thus also important in terms of strengthening and enhancing Slovenia’s recognition and reputation within the international scientific community. 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 at University of Ljubljana and transfer their knowledge to students. 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 hightech  biotechnological companies that has been a priority for the Slovenian economic
Most important scientific results Annual report 2015, interim report, final report
Most important socioeconomically and culturally relevant results Annual report 2015, interim report, final report
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