Projects / Programmes
Modelling of structure property relationships QSAR QSPR
January 1, 2004
- December 31, 2008
| 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 |
|
QSAR, Chemometrics, Chemical structure, Structural descriptors, Linear and non-linear models, Neural networks, Graph theory, Drug design, Toxicity, Data bases, Spectroscopic methods, Combined analytical techniques, Metrology, Nucleozides, Oligonucleotides, Triple helix, G-quadroplexes Pt(II)- anticancer drugs, antiviral drugs, ionophores, nanotubes, kalix(4)aren, Beta cyclodextrin
Researchers (18)
Organisations (2)
Abstract
The central object of the research program is chemical structure, which is bounded to the research of structure - property relationship, as well as to the field of structural chemistry and chemical analysis. Computational methods for the determination of molecular descriptors, i.e. numerical parameters reflecting specific information of molecular structure, are studied in order to characterize chemical structure of compounds. These descriptors are known as constitutional, geometric, electrostatic, quantum-chemical, and topologic descriptors. In thesearch for the most suitable structure representations various chemometrics methods are studied and used: transformations, mapping, clustering, and variable selection methods. Besides the chemical structure we are interested in compounds' properties: pharmacological properties in the field of drug design and synthesis and toxic ones in the field of risk assessment of chemicals for environment and food safety. With the research of linear and non-linear models linking multi-variate description of structures with properties we would like to determine as detailed as possible the relationship between chemical structure and property of compounds. The aim of the theoretical study of structure - activity (property) relationship (QSAR-QSPR) is to explain the reaction mechanism of binding ligands to receptors (in the case of pharmacological and toxic properties) and to yield finally the assessment of compounds property on the basis of its chemical structure. In the frame of the research program the theoretical methods are linked to the experimental ones when characterizing the structures of compounds synthesized within the laboratory. The most important are NMR spectroscopy, hyphenated analytical techniques, LC-MS, and GC-MS.
A considerable part of the research is the development of new chemometrics methods and their application and testing in a broad research field from metrology to process engineering, and archaeology.
Significance for science
The increasing concern for the environment in the broadest sense (air, water, food) has enlarged the need for the assessment of harmful environmental impact of chemicals. The EU regulations demand the assessment of the toxicity for every new chemical on the market. The Chemicals Bureau responsible for the task makes the assessment on the basis of the available data or eventually requires additional biological tests. To this procedure the QSAR models are alternative methods, which may save time and money. The research of methods in the field of structure - property relationship also help to resolve the mechanisms of action of toxic compounds. The results of the research in the program "Modelling of structure - property relationships QSAR-QSPR" are relevant for a broad international area not only for the research, but have impact on the quality of life in almost every aspect. Research directions are in accordance with the research priorities in Slovenia and Europe, i.e. genomics, biotechnology for health, quality and safety of food, sustainable development, and information technology. Our research in the directions of EU priorities can be confirmed with the involvement of our Laboratory into several European projects, in past, such as Tempus, Copernicus, Virtual Institute VICIM, Training networks – IMAGETOX, and Marie Curie Training Site (in two involved laboratories). The collaboration in new, on-going EU projects (IBAAC - MCTN, TRACE - IP, CAESAR - STREP) confirm the relevance of our research work in a larger time scale and the competence of our research team, what makes us a credible partner in the projects. The participation in the past and new projects makes the contacts with foreign research groups and outstanding scientists firm enough to enable excellent basis for further development of chemometrics. The collaboration in TRACE project enabled us to contribute to investigate the traceability of food. The identification of food origin and the traceability is one of the major interests of producers, food industry, marketing and consumers, i.e. the traceability along entire fork to farm food chains. The traceability of food is based on the methods described in this proposal and have been used on several data sets in case studies performed in the laboratory during several years. Several bilateral projects (with USA, India Russia, Macedonia) show the interest of the involved counties in the research of our group. The content of CAESAR project (Computer-Assisted Evaluation of industrial chemical Substances According to Regulations) is of especial interest in the sense of care for environment, which is a world trend. The OECD (Organization for Economic Co-operation and Development) recommends to the member states a support of QSAR research in the assesment of toxicity of substances.
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. The research is directed towards the encouragement of Slovenian pharmaceutical industry, which is now stuck in the profit driven development of generic products, towards the development of new drugs. The other contribution important for socio-economic development of Slovenia is traceability of food developed on chemometrics methods for evaluation of the results of chemical analyses (Slovenian food industry). The research program is involved in the educational programs of the universities and institutes, besides, it encompass the industrial problems of development and quality control. We collaborate with the University of Ljubljana with courses "Chemometrics" and "Artificial Intelligence" in the frame of graduate and post-graduate studies on FKKT, University of Ljubljana. We collaborate also with the University of Maribor in the field of modelling evaluation of analytical results, coding of chemical structures, spectral analysis, etc. We are involved in the preparation of life-long learning program at University of Maribor with courses on statistics and chemometrics. At Agriculture Faculty of the University of Maribor we contribute a course »Artificial intelligence in agriculture«. At University of Maribor, Faculty of Civil Engineering, we contribute a course »Materials for Engineering«. At the level of transfer of knowledge into practise we are involved in the program of qualification of asphalt builders organised by the Slovenial roads organisation. The program is educationally oriented, so that it enables the diploma work, master and PhD projects. In the Slovenian economy the needs for the described research are present especially in the pharmaceutical, chemical, and food industry. The largest interest up to now was expressed for the experimental design, data mining, evaluation of analytical results, and optimization of industrial procedures. In the program several directions are open, possibly adaptable to individual industrial problems. We had a successful collaboration with several Slovenian companies. A recent project for Slovenian industrial partner is a study on »Granulocyte Colony-Stimulating Factor«, which is potential biopharmaceutical. A chemometrics study was performed for a comparison of protein structure in original drug, and a procedure was proposed, which would eventually confirm structural identity of the two investigated proteins. The program encompassed also the statistical treatments and evaluations needed for a good laboratory practice, which is unavoilable for the acreditation of industrial laboratories, necessary in the demanding European market. For Slovenia the fast transfer of knowledge into practice is of great importance. Planned workshops and seminars from the field of Chemometrics, QSAR, QSPR, Structural Chemistry, and Spectroscopy will help to adapt quickly to new trends in the world. Our Schools of Chemometrics have already a tradition in Slovenia. The lecturers from abroad (NL, E, IT, DE, BE) presented their knowledge and experience to slovenian participants. The members of our research group were lecturing at many foreign universities and institutions like UNIDO. Presentations at international scientific conferences are the opportunity for the dissimination of knowledge acquired during the past period, which is important for the affirmation of Slovenia in the world.
Most important scientific results
Final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Final report,
complete report on dLib.si
