Projects / Programmes
Modeliranje kemijskih procesov in lastnosti spojin (Slovene)
January 1, 2009
- December 31, 2014
| Code |
Science |
Field |
Subfield |
| 1.04.00 |
Natural sciences and mathematics |
Chemistry |
|
| 1.09.00 |
Natural sciences and mathematics |
Pharmacy |
|
| 1.01.00 |
Natural sciences and mathematics |
Mathematics |
|
| Code |
Science |
Field |
| 1.04 |
Natural Sciences |
Chemical sciences |
Researchers (18)
Organisations (2)
Significance for science
The research program is in accordance with the guidelines of the development of science in Slovenia and abroad (genomics, personalized health care PHC, quality and food safety, sustainable development). Part of the research relates to the assessment of the impact of chemicals on the environment, human and animal health. Alternative methods that are being developed reduce the expenses in terms of costs, time, and laboratory animal sacrifices. The proposed QSAR methods in combination with molecular modelling allow elucidating the mechanism of action of toxic chemicals, which is important not only for the registration of chemicals, but is also one of the most difficult steps in the drug design, as the side effects of the new drug may be the reason that the product is rejected at the stage of biological testing. Cheminformatics methods, which we do not only use, but also develop in the framework of proposed research, have an important role in filling the information gaps in the field of chemical registration for regulatory purposes (lack of data on biological properties from in vitro and in vivo tests) and in the field of protein 3D structure elucidation. During the last years, the number of proteins with the resolved 3D structure, either by new crystallography or NMR spectroscopy data, has substantially increased. However, the structure elucidation of transmembrane proteins still remains a big issue. For that reason a part of the proposed research is focused on the investigation of membrane proteins. Any progress in the methodology for prediction of 3D structures of membrane proteins would be a great step towards the secondary structure resolution of those proteins that are difficult to be experimentally characterized due to known problems with solubility, crystallisation, or synthesis/expression. The proposed combined approach of molecular and chemometrics modelling on the basis of ligands (substrates) with or without host protein information facilitates to overcome the problems with the initial hypothetical 3D structure, which is particularly important in case of protein without homologue structures in PDB database. We’ll try to fill the information gap of transmembrane protein structures employing in silico methods combined with the constraints from the experimental data. Membrane proteins that facilitate the transport of organic compounds through the cell membrane into intracellular space are particularly interesting for their association with some malignant tumours. These proteins are thus an important target in the research of drug formulation. Bilitranslocase is such target protein, basically involved in the transport of bilirubin from blood circulation to liver cells. We have already found out that bilitranslocase is a potential drug transporter; in future we will try to show how the anticancer drugs might be specifically delivered to certain tumours in which the bilitranslocase is upregulated. On this way lower doses of drugs would be needed and consequently the side effects would be diminished. The results would have a great potential for further drug development. In the framework of the research on the asphalt mixtures where the properties of bitumen in the asphalt layers are explored deficiencies in some standardized methods are often found. Through the membership in the European standardization committee CEN ((CEN/TC 227 for road materials / WG1 – working group for asphalt mixtures) we spread our findings into the international arena. Introducing the chemometrics methods to the field of asphalt industry will enable the transfer of knowledge between research and technology.
Significance for the country
The principles of the research program represent the basis for a successful optimisation of properties of designed and newly synthesized potential drugs. While the Slovenian pharmaceutical industry is focused mainly to the production and development of generic drugs the trends in Europe’s research seems to be different. Some of the health problems like the occurrence of microbes resistant to antibiotic, or increase of neurodegenerative diseases become a general health concern. Therefore, the European Commission in the project HORIZON 2020 supports the pharmaceutical industry to the research and development of new drugs in these areas. Our ambition is to include Slovenia into this research, because the product's added value can be enlarged only by the innovativeness and with the discovery of completely new drugs. The proposed research field is complex, but feasible in the interdisciplinary approach if partially supported by the Europe. The other contribution important for socioeconomic development of Slovenia resides in promotion, development and application of QSAR models (in silico methods) for evaluation of toxic and eco-toxic properties of compounds, which is connected with the growing care for environment. European chemical legislation REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) pays special attention to the using of alternative methods to animal experiments for estimation of toxicity and the QSAR is a part of this strategy. QSAR models not only help assessing toxicity of chemicals but also in explaining the mechanisms of toxicity. Currently, the research group is involved in two EU projects on this topic: PROSIL and COSMOS. PROSIL (LIFE+) stimulates a proactive approach of the industry to assess their products by in silico methods and at the same time search for a supplement of hazardous products with environmentally more acceptable ones. COSMOS is a project within the SEURAT cluster, which is dedicated to development of alternative methods for cosmetic ingredients and is a half financed from Cosmetics Europe. We will disseminate the knowledge to Slovenian industry through workshops organized together with the Chamber of Commerce and the Chemical Bureau of the Republic of Slovenia. In Slovenia we are partners of informal group on hormone disrupters, which is coordinated from Institute of public health, Ljubljana. The members meet occasionally and discuss the reports and documents issued from European Chemical Agency (ECA), Organisation for Economic Cooperation and Development (OECD), and Joint Research Centre (JRC). As partners in EU project we share the expertise and promote the European politics in regulation of chemicals (REACH) and thus also promote Slovenia. The knowledge and experiences from EU projects are also disseminated and promoted in Slovenia. The development and implementation of the optimization methods using mapping technique based on feed forward bottle-neck neural network (simple in use, not time consuming) enables an increasing of the quality of products, reduction of energy consumption, reduction of waste, reduction of operation costs, increasing the productivity.
Most important scientific results
Annual report
2009,
2010,
2011,
2012,
2013,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2009,
2010,
2011,
2012,
2013,
final report,
complete report on dLib.si
