Access Path to the Ligand Binding Pocket May Play a Role in Xenobiotics Selection by AhR.

ABSTRACT: Understanding of multidrug binding at the atomic level would facilitate drug design and strategies to modulate drug metabolism, including drug transport, oxidation, and conjugation. Therefore we explored the mechanism of promiscuous binding of small molecules by studying the ligand binding domain, the PAS-B domain of the aryl hydrocarbon receptor (AhR). Because of the low sequence identities of PAS domains to be used for homology modeling, structural features of the widely employed HIF-2α and a more recent suitable template, CLOCK were compared. These structures were used to build AhR PAS-B homology models. We performed molecular dynamics simulations to characterize dynamic properties of the PAS-B domain and the generated conformational ensembles were employed in in silico docking. In orde

SUBMITTER: Szollosi D 

PROVIDER: S-EPMC4699818 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature