Martin Smieško graduated in medicinal chemistry from the Faculty of Pharmacy of Comenius University, Bratislava, Slovakia in 1999. In 2003 he obtained his PhD. at the same university with his thesis focusing on Molecular Modeling of ACE inhibitors. After that he joined the group of Dr. Emilio Benfenati at the Institute of Pharmacological Research "Mario Negri" in Milano, Italy, where he worked 2 years as a post-doctoral fellow on the development of QSAR models for ecotoxicology. Then he spent one year at biotech company anterio consult & research in Mannheim, Germany focusing on the in silico development of synthetic receptor scaffolds for chiral separations. In September 2006 Martin joined the group of Prof. Angelo Vedani at the Molecular Modeling Group at the Department of Pharmaceutical Sciences, University of Basel as a research associate. In April 2014 he received the "Habilitation" and was promoted to "Privatdozent" (Senior Lecturer) in the field of Computer-Aided Drug Discovery and Toxicology. In years 2016-2019 he was appointed an interim group leader of the Molecular Modeling Group. In August 2019 he became a member of the newly formed Computational Pharmacy Group as a senior research scientist. He is the co-developer of the in silico screening platform VirtualToxLab and co-author of more than 70 scientific publications. His main areas of interest include molecular simulations of nuclear receptors, cytochromes P450 and carbohydrates.
OpenTox Euro 2019 workshop: Building of Predictive Models for IATAs
Computational methods implemented in the predictive models for evaluation of small molecule-protein interaction have fully matured thanks to rapid development in recent decades and nowadays can be routinely used for toxicity profiling. Predictive modeling offers a complete “virtualization” of the toxicity assessment with benefits in terms of speed, reduced costs as well as replaced animal testing (3R). The regulatory segment therefore urges for stronger integration of in silico tools in decision making with the vision to replace experimental profiling in the long run.
The aim of the workshop is to introduce various established computational approaches used for building of predictive models and help the participants in exploring their capabilities using selected examples. We will provide a brief overview on how to identify necessary resources and information for the target of interest (e.g. on-line services, available software, protein structures and ligand affinity data), develop similarity-, ligand- or structure-based predictive models and how to validate them. We will also provide the opportunity to evaluate compounds of interest with some of the freely available in silico tools. And finally, we will offer a few critical recommendations on how to draw conclusions from computational predictions.
OpenTox Euro 2019 session 4 overview: In Silico Modelling
In the last two decades, various in silico methods have been tightly integrated in the drug discovery and development pipelines of the pharmaceutical industry. Despite their huge potential, the integration of computational approaches to toxicity prediction often does not reach beyond predictions based on quantitative-structure relationships or read-across. Our session has the ambition to present – using a variety of interesting examples – current possibilities of established molecular modeling techniques in toxicity prediction within regulatory, academic as well as industrial settings. Selected presentations will address topics ranging from the toxicokinetic and off-target compound profiling, through comprehensive simulations at one particular target approaching at the limits of personalized toxicology to multiscale modeling of drug mechanisms and safety.
OpenTox Euro 2019 talk: Large-scale in silico toxicity profiling of compounds contained in printing inks for food packaging materials
Providing sustainable and safe nutrition to the population is one of the main tasks of the modern food industry. While food packaging materials fulfill their invaluable protective role, certain substances can migrate from them into food. Switzerland is worldwide the only country, in which substances in printing inks for food packaging are regulated.
In the order to identify potentially harmful compounds, we performed a virtual screening study along with a complex toxicokinetic characterization of more than three thousand chemical compounds contained in printing inks. This screening was performed in collaboration with the main Swiss regulatory authority.
Around two percent of the screened compounds were found to fulfill toxicokinetic criteria and predicted to bind with high affinity to at least one of the nuclear receptors. To validate the predictions, the most relevant hits were forwarded for experimental in vitro testing. Within this presentation, strengths and weaknesses of the applied in silico techniques will be critically discussed based on the most interesting examples.