Molecular Diversity

, Volume 13, Issue 3, pp 321–336 | Cite as

Similarity-based SIBAR descriptors for classification of chemically diverse hERG blockers

Full Length Paper

Abstract

There is an increasing interest in computational models for the classification and prediction of the human ether-a-go-go-related-gene (hERG) potassium channel affinity in the early phase of drug discovery and development. In this study, similarity-based SIBAR descriptors were applied in order to develop and validate in silico binary QSAR and counter-propagation neural network models for the classification of hERG activity. The SIBAR descriptors were calculated based on four reference datasets using four sets of 2D- and 3D-descriptors including 3D-grid-based VolSurf, 3D ‘inductive’ QSAR, Van der Waals surface area (P_VSA) and a set of 11 hERG relevant 2D descriptors devised from feature selection methods. The results indicate that the reference data set tailored to the specific problem, together with a set of hERG relevant descriptors, provides highly predictive models.

Keywords

hERG SIBAR Classification Counter-propagation neural networks Antitarget Similarity-based descriptor 

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Emerging Field Pharmacoinformatics, Department of Medicinal ChemistryUniversity of ViennaViennaAustria
  2. 2.Department of Pharmaceutical Chemistry, School of PharmacyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam

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