title: Virtual screening applications in short-chain dehydrogenase/reductase research.
abstract: Several members of the short-chain dehydrogenase/reductase (SDR) enzyme family play fundamental roles in adrenal and gonadal steroidogenesis as well as in the metabolism of steroids, oxysterols, bile acids, and retinoids in peripheral tissues, thereby controlling the local activation of their cognate receptors. Some of these SDRs are considered as promising therapeutic targets, for example to treat estrogen-/androgen-dependent and corticosteroid-related diseases, whereas others are considered as anti-targets as their inhibition may lead to disturbances of endocrine functions, thereby contributing to the development and progression of diseases. Nevertheless, the physiological functions of about half of all SDR members are still unknown. In this respect, in silico tools are highly valuable in drug discovery for lead molecule identification, in toxicology screenings to facilitate the identification of hazardous chemicals, and in fundamental research for substrate identification and enzyme characterization. Regarding SDRs, computational methods have been employed for a variety of applications including drug discovery, enzyme characterization and substrate identification, as well as identification of potential endocrine disrupting chemicals (EDC). This review provides an overview of the efforts undertaken in the field of virtual screening supported identification of bioactive molecules in SDR research. In addition, it presents an outlook and addresses the opportunities and limitations of computational modeling and in vitro validation methods.
authors.affiliation: Swiss Center for Applied Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Katharina R
authors.initials: KR
authors.lastname: Beck
authors.affiliation: Institute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), Computer Aided Molecular Design Group, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Teresa
authors.initials: T
authors.lastname: Kaserer
authors.affiliation: Institute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), Computer Aided Molecular Design Group, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: Daniela.Schuster@uibk.ac.at.
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.affiliation: Swiss Center for Applied Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland. Electronic address: Alex.Odermatt@unibas.ch.
authors.forename: Alex
authors.initials: A
authors.lastname: Odermatt
mesh_terms: D000818:Animals; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000639:trends; D019295:Computational Biology; D017076:Computer-Aided Design / Q000639:trends; D062126:Databases, Chemical; D015195:Drug Design; D052244:Endocrine Disruptors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D005103:Expert Systems; D057166:High-Throughput Screening Assays / Q000639:trends; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D000069550:Machine Learning; D062105:Molecular Docking Simulation / Q000639:trends; D011487:Protein Conformation; D013379:Substrate Specificity; D014116:Toxicology / Q000379:methods / Q000639:trends; D054928:Validation Studies as Topic
chemical_list: D052244:Endocrine Disruptors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D006913:Hydroxysteroid Dehydrogenases
keywords: Drug development; Endocrine disrupting chemicals; Hydroxysteroid dehydrogenase; Short-chain dehydrogenase/reductase; Virtual screening