title: OpenVirtualToxLab--a platform for generating and exchanging in silico toxicity data.
abstract: The VirtualToxLab is an in silico technology for estimating the toxic potential--endocrine and metabolic disruption, some aspects of carcinogenicity and cardiotoxicity--of drugs, chemicals and natural products. The technology is based on an automated protocol that simulates and quantifies the binding of small molecules towards a series of currently 16 proteins, known or suspected to trigger adverse effects: 10 nuclear receptors (androgen, estrogen α, estrogen β, glucocorticoid, liver X, mineralocorticoid, peroxisome proliferator-activated receptor γ, progesterone, thyroid α, thyroid β), four members of the cytochrome P450 enzyme family (1A2, 2C9, 2D6, 3A4), a cytosolic transcription factor (aryl hydrocarbon receptor) and a potassium ion channel (hERG). The toxic potential of a compound--its ability to trigger adverse effects--is derived from its computed binding affinities toward these very proteins: the computationally demanding simulations are executed in client-server model on a Linux cluster of the University of Basel. The graphical-user interface supports all computer platforms, allows building and uploading molecular structures, inspecting and downloading the results and, most important, rationalizing any prediction at the atomic level by interactively analyzing the binding mode of a compound with its target protein(s) in real-time 3D. Access to the VirtualToxLab is available free of charge for universities, governmental agencies, regulatory bodies and non-profit organizations.
authors.affiliation: Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland; Foundation Biographics Laboratory 3R, Klingelbergstrasse 50, 4056 Basel, Switzerland. Electronic address: angelo.vedani@unibas.ch.
authors.forename: Angelo
authors.initials: A
authors.lastname: Vedani
authors.affiliation: Foundation Biographics Laboratory 3R, Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Max
authors.initials: M
authors.lastname: Dobler
authors.affiliation: Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Zhenquan
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Smieško
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D054715:Cardiotoxins / Q000633:toxicity; D006801:Humans; D033181:Information Dissemination / Q000379:methods*; D020407:Internet; D008958:Models, Molecular; D011487:Protein Conformation; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D012984:Software; D014116:Toxicology / Q000639:trends*
chemical_list: D002273:Carcinogens; D054715:Cardiotoxins; D018160:Receptors, Cytoplasmic and Nuclear
keywords: 3D simulations; In silico toxicology; Mechanistic interpretation; Open-access platform; Protein-mediated adverse effects