Modeling of the Aryl Hydrocarbon Receptor (AhR) Ligand Binding Domain and Its Utility in Virtual Ligand Screening to Predict New AhR Ligands

J. Med. Chem., 2009, 52 (18), pp 5635–5641
DOI: 10.1021/jm900199u
Publication Date (Web): August 31, 2009

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor; the AhR Per-AhR/Arnt-Sim (PAS) domain binds ligands. We developed homology models of the AhR PAS domain to characterize previously observed intra- and interspecies differences in ligand binding using molecular docking. In silico structure-based virtual ligand screening using our model resulted in the identification of pinocembrin and 5-hydroxy-7-methoxyflavone, which promoted nuclear translocation and transcriptional activation of AhR and AhR-dependent induction of endogenous target genes.

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