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| About Artem Cherkasov (University of British Columbia) |
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Dr. Artem Cherkasov is an Assistant Professor in the Faculty of Medicine at the University of British Columbia. He joined the Infectious Diseases Division at the UBC Faculty of Medicine in February 2003 where his research focuses on developing and applying bioinformatics tools in drug design, molecular modeling, and bioinformatics.
He received undergraduate and graduate training in chemistry from Kazan State University (Kazan, Russia). Dr. Cherkasov obtained his Ph.D. in 1996 from the Russian Academy of Science. In 2001 Dr. Cherkasov became one of the youngest recipients (29 y/o) of the Russian Academy of Science’s secondary level Doctor of Science degree, typically a late-stage-career achievement.
From 1998 until 2000, Dr. Cherkasov held postdoctoral positions in the Royal Institute of Technology in Stockholm, Sweden, and the University of Saskatchewan, Canada. In 2001 he joined the BC Cancer Research Centre’s BC Genome Sciences Centre as a Research Associate.
Dr. Cherkasov’s research interests include computer-aided drug design, applications of artificial intelligence in structure-activity modeling for bioactive substances, development of large-scale bioinformatics and genomics tools and molecular modeling techniques. He is the author of more than 100 scientific articles in peer reviewed journals, conference proceedings and patents.
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The Use of Conventional Drug Design Technologies for Identification of Potential Endocrine Disruptors Interacting with Sex-Hormone Binding Globulin in Zebra Fish
Artem Cherkasov, University of British Columbia
Anthropogenic compounds with the capacity to interact with the steroid-binding site of sex hormone binding globulin (SHBG) pose health risks to humans and other vertebrates including fish. Building on studies of human SHBG, we have applied in silico drug discovery methods to identify potential binders for SHBG in zebrafish (Danio rerio) as a model aquatic organism. Computational methods, including; homology modeling, molecular dynamics simulations, virtual screening, and 3D QSAR analysis, successfully identified 6 non-steroidal substances from the ZINC chemical database that bind to zebrafish SHBG (zfSHBG) with low-micromolar to nanomolar affinities, as determined by a competitive ligand-binding assay. We also screened 80,000 commercial substances listed by the European Chemicals Bureau and Environment Canada, and 6 non-steroidal hits from this in silico screen were tested experimentally for zfSHBG binding. All 6 of these compounds displaced the [3H]5α-dihydrotestosterone used as labeled ligand in the zfSHBG screening assay when tested at a 33 μM concentration, and 3 of them (hexestrol, 4-tert-octylcatechol, and dihydrobenzo(a)pyren-7(8H)-one) bind to zfSHBG in the micromolar range. The study demonstrates the feasibility of large scale in silico screening of anthropogenic compounds that may disrupt or highjack functionally important protein:ligand interactions. Such studies could increase the awareness of hazards posed by existing commercial chemicals at relatively low cost.
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