title: Pred-hERG: A Novel web-Accessible Computational Tool for Predicting Cardiac Toxicity.
abstract: The blockage of the hERG K(+) channels is closely associated with lethal cardiac arrhythmia. The notorious ligand promiscuity of this channel earmarked hERG as one of the most important antitargets to be considered in early stages of drug development process. Herein we report on the development of an innovative and freely accessible web server for early identification of putative hERG blockers and non-blockers in chemical libraries. We have collected the largest publicly available curated hERG dataset of 5,984 compounds. We succeed in developing robust and externally predictive binary (CCR≈0.8) and multiclass models (accuracy≈0.7). These models are available as a web-service freely available for public at http://labmol.farmacia.ufg.br/predherg/. Three following outcomes are available for the users: prediction by binary model, prediction by multi-class model, and the probability maps of atomic contribution. The Pred-hERG will be continuously updated and upgraded as new information became available.
authors.affiliation: Labmol - Laboratory for Molecular Modeling and Drug Design, Faculty of Pharmacy, Federal University of Goias, Goiania, Goiás 74605-170, Brazil phone: +55 62 3209-6451; fax: +55 62 3209-6037.|Chemistry Institute, Federal University of Goias, P. O. Box 131, Goiania, Goiás 74001-970, Brazil.
authors.forename: Rodolpho C
authors.initials: RC
authors.lastname: Braga
authors.affiliation: Labmol - Laboratory for Molecular Modeling and Drug Design, Faculty of Pharmacy, Federal University of Goias, Goiania, Goiás 74605-170, Brazil phone: +55 62 3209-6451; fax: +55 62 3209-6037.
authors.forename: Vinicius M
authors.initials: VM
authors.lastname: Alves
authors.affiliation: Labmol - Laboratory for Molecular Modeling and Drug Design, Faculty of Pharmacy, Federal University of Goias, Goiania, Goiás 74605-170, Brazil phone: +55 62 3209-6451; fax: +55 62 3209-6037.
authors.forename: Meryck F B
authors.initials: MF
authors.lastname: Silva
authors.affiliation: Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Muratov
authors.affiliation: Department of Chemistry, Bioinformatics Research Center, North Carolina State University, Raleigh, NC, 27695, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Fourches
authors.affiliation: Chemistry Institute, Federal University of Goias, P. O. Box 131, Goiania, Goiás 74001-970, Brazil.
authors.forename: Luciano M
authors.initials: LM
authors.lastname: Lião
authors.affiliation: Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tropsha
authors.affiliation: Labmol - Laboratory for Molecular Modeling and Drug Design, Faculty of Pharmacy, Federal University of Goias, Goiania, Goiás 74605-170, Brazil phone: +55 62 3209-6451; fax: +55 62 3209-6037. carolina@ufg.br.
authors.forename: Carolina H
authors.initials: CH
authors.lastname: Andrade
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000378:metabolism; D054715:Cardiotoxins / Q000737:chemistry* / Q000633:toxicity; D003198:Computer Simulation; D062126:Databases, Chemical; D000072237:ERG1 Potassium Channel / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D006801:Humans
chemical_list: D054715:Cardiotoxins; D000072237:ERG1 Potassium Channel; C000606913:KCNH2 protein, human
keywords: QSAR models; Screening; hERG; web-Server