Hybrid scoring and classification approaches to predict human pregnane X receptor activators.

Pharmaceutical Research
Sandhya KortagereSean Ekins

Abstract

The human pregnane X receptor (PXR) is a transcriptional regulator of many genes involved in xenobiotic metabolism and excretion. Reliable prediction of high affinity binders with this receptor would be valuable for pharmaceutical drug discovery to predict potential toxicological responses Computational models were developed and validated for a dataset consisting of human PXR (PXR) activators and non-activators. We used support vector machine (SVM) algorithms with molecular descriptors derived from two sources, Shape Signatures and the Molecular Operating Environment (MOE) application software. We also employed the molecular docking program GOLD in which the GoldScore method was supplemented with other scoring functions to improve docking results. The overall test set prediction accuracy for PXR activators with SVM was 72% to 81%. This indicates that molecular shape descriptors are useful in classification of compounds binding to this receptor. The best docking prediction accuracy (61%) was obtained using 1D Shape Signature descriptors as a weighting factor to the GoldScore. By pooling the available human PXR data sets we revealed those molecular features that are associated with human PXR activators. These combined computation...Continue Reading

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Citations

May 2, 2013·Neuropharmacology·Sandhya KortagereOle Valente Mortensen
Apr 30, 2010·Journal of Chemical Information and Modeling·Sandhya KortagereLawrence W Bergman
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Jun 19, 2010·Environmental Health Perspectives·Sandhya KortagereSean Ekins
Dec 17, 2009·PLoS Computational Biology·Sean EkinsMatthew D Krasowski
Dec 24, 2013·Journal of Pharmacological and Toxicological Methods·Sean Ekins
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Feb 24, 2010·Journal of Pharmacological and Toxicological Methods·Sandhya Kortagere, Sean Ekins
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Feb 4, 2009·Trends in Pharmacological Sciences·Sandhya KortagereSean Ekins
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Mar 21, 2017·Journal of Pharmaceutical Sciences·Nao Torimoto-KatoriMenghang Xia
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Jun 10, 2010·Journal of Chemical Information and Modeling·Lisa Michielan, Stefano Moro
May 23, 2015·Journal of Chemical Information and Modeling·Alex M ClarkSean Ekins
Nov 16, 2017·ACS Chemical Neuroscience·Sandhya KortagereAndréia C K Fontana
Jun 12, 2019·ACS Chemical Neuroscience·Shaili AggarwalOle V Mortensen

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