In September 2011 we organized international conference CMTPI (Computational Methods in Toxicology and Pharmacology Integrating Internet Resources), Maribor, September 37, 2011. It was the sixth CMTPI conference after Bordeaux, Thessaloniki, Shanghai, Moscow, and Istanbul. The Symposium covered the following fields: the Internet as a source of chemical information, (Q)SAR, QSPR modelling in drug discovery, computer modelling (QSAR) of ecotoxicological properties, which are important in the registration of chemicals (legislation REACH). Presented were: six plenary lectures, 30 oral presentations and 32 posters. The members of our laboratory presented, in collaboration with different partners, five oral presentations and eight posters. In one of the lectures we presented the toxicological information resources available on the Internet in Slovenia. In the first part we present Slovenian Universities and their curricula which are touching the toxicology. In the second part we present the Governmental Agencies, which are responsible to control the chemical market, the Chemical Office of R Slovenia and the Phytosanitary Administration of R Slovenia. We checked the availability of information about the chemical substances and about the regulatory status of chemicals. The web pages have links to European bodies responsible for regulation, ECHA, Biocides, EUSES, IUCLIO, ESIS, EINECS,HPVLPV, REACH,CLEEN and to Slovenian documentation, like Slovenian laws and bills, risk assessments, etc. The Phytosanitary Administration has links to the database with producers and traders of pesticides and database on pesticide toxicities. The third group represents the research institutes and public institutes. The basic task of the research institutes is the research and education and some projects are dedicated to environment and toxicity. From public institutes the Institute of public health plays the central role in toxicity issues. One of its departments is the Chemical safety department. It provides the basic information and basic lectures on toxicity and the links toweb pages to European agencies like ECB, EFSA, to member state agencies like Bundesinstitute fuer Risikobewertung, food UK, to USA agencies like EPA, FDA, TOXNET and to Slovenian legislation pages. Another important department of the Institute is Drug safety department. It has a link to a database of all drugs registered for use in Slovenia.
B.01 Organiser of a scientific meeting
COBISS.SI-ID: 4777754The transmembrane proteins are integral membrane proteins with one or more segments that span the entire biological membrane. They are essential in maintaining the normal cell physiology, playing vital roles in ligand transport, cell signaling, energy production, immunity etc. Besides, the transmembrane proteins are important drug targets and are responsible for their carriermediated active uptake. A rough estimate suggests around 25% of the sequenced genome to code for transmembrane proteins. Nevertheless, the present knowledge about the transmembrane protein sequences and their classification remains incomplete. Moreover, due to experimental difficulties, the structural and functional details of the known transmembrane proteins are vastly underexplored. Considering the biological and pharmaceutical interest, several in silico methods are developed and applied, in combination with experimental methods, towards elucidating the structural details and functional mechanisms of the transmembrane proteins. The research work presented in this thesis is focused on developing transmembrane prediction algorithms. Identifying the transmembrane regions is the preliminary step towards detailed structural understanding of a transmembrane protein. The next part of the thesis is directed towards the structural elucidation of bilitranslocase, an organic anion transporter protein. It is a 340 amino acids long transmembrane protein with no available structural information. To identify the transmembrane regions of bilitranslocase, the developed transmembrane region prediction algorithm is used. Later, the stability of the predicted transmembrane domains are assessed using molecular dynamics simulations. The probable arrangements of transmembrane domains are studied, which identifies the most populated and energetically favourable arrangement types. NMR studies are performed to obtain the 3D structures of the transmembrane domains playing central role in the transport mechanism. The work analyzes and discusses in details the possible functional importance of the bilitranslocase structural details obtained from the theoretical and NMR experiments.
D.09 Tutoring for postgraduate students
COBISS.SI-ID: 268364288Issue dedicated to Professor Milan Randić at his 80th anniversary. MN, program P10017 leader, edited the special issue (17 papers dedicated to Prof. Milan Randić) and wrote the preface.
C.04 Editorial board of an international magazine
The target of the presented research is Cathepsin K (Cat K), a lysosomal cysteine protease that plays an important role in many severe diseases, which makes inhibition of Cat K a potentially attractive therapeutic approach. Several compounds, including balicatib, passed preclinical studies and were tested in clinical trials as perspective Cat K inhibitors. Balicatib proved as a potent inhibitor, however, the side effects caused by the accumulation of drug candidate in the lysosomes of human skin fibroblast as a consequence of its basic nature prevented further drug development. We have introduced a combination of chemometrics and virtual combinatorial library approaches employed in order to better assess the correlation between molecular structure and biological activity (Cat K inhibition) of benzamidecontaining aminonitriles and predict potential new inhibitors with less side effects connected to basic nature of some clinically trailed drug candidates. A QSAR model was constructed based on the Counterpropagation artificial neural network (CPANN), which was trained with a set of diversely substituted aminonitriles of known experimentally determined activities. Interpretation of selected molecular descriptors was performed by evaluation of overlapping contours of the Kohonen levels with the CPANN response surface and with clusters of objects in the Kohonen topmap (SOM). The developed QSAR model is proposed to be used to design new nontoxic Cat K inhibitors. The synthesis of predicted most potent inhibitors is in progress and will be subjected to additional testing.
B.04 Guest lecture
COBISS.SI-ID: 36971781The subject of invention is the asphalt with the addition of PMMA / ATH composite powder, which replaces the filler or is a supplement to the filler. PMMA / ATH composite powder is added according to the invention to the filler to improve properties of asphalt mixtures. The invention falls within the scope of asphalt. The filler is the smallest sand fraction in the asphalt mixture with standardized sieving curve. Asphalt mixture according to the invention contains in weight percentage from 3% to 8% of binder, from 75% to 94% of stone aggregate with a particle size greater than the grain size of filler, from 0 % to 17% of filler, and from 0.5 to 17% of PMMA / ATH composite powder.
F.32 International patent
COBISS.SI-ID: 4621850