Comparative analysis of interactions between aryl hydrocarbon receptor ligand binding domain with its ligands: a computational study

Aryl hydrocarbon receptor (AhR) ligands may act as potential carcinogens or anti-tumor agents. Understanding how some of the residues in AhR ligand binding domain (AhRLBD) modulate their interactions with ligands would be useful in assessing their divergent roles including toxic and beneficial effects. To this end, we have analysed the nature of AhRLBD interactions with 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), 6-formylindolo[3,2-b]carbazole (FICZ), indole-3-carbinol (I3C) and its degradation product, 3,3′-diindolylmethane (DIM), Resveratrol (RES) and its analogue, Piceatannol (PTL) using molecular modeling approach followed by molecular dynamic simulations. Results showed that each of the AhR ligands, TCDD, FICZ, I3C, DIM, RES and PTL affect the local and global conformations of AhRLBD. The data presented in this study provide a structural understanding of AhR with its ligands and set the basis for its functions in several pathways and their related diseases.