Computational Modeling of AhR Ligand Binding

The ligand-binding affinity of 3 indolimine analogs, including I-200, I-214, and I-248, was investigated using Autodock Tools 4 and Autodock Vina, and a cryo-EM structure-based computational model of the human AHR PAS B domain [9 (link),20 (link),21 (link),22 (link),23 (link)]. Docking models for the 3 indolimine ligands were built and minimized using PyMOL Molecular Graphics System, Version 2.52 Schrödinger, and LLC and all models were optimized for docking using Autodock Tools [24 ]. Autodock Vina was run using standard settings, using Grid box parameters generated in Autogrid for a 30 ų docking grid centered on the indirubin binding site, as described previously [25 (link)]. Docking results were analyzed using Autodock Tools 4 and The PyMOL Molecular Graphics System, Version 2.52. As shown in Supplementary Table S2, AHR docking model quality was validated using an Autodock Vina re-docking analysis with the structural coordinates of indirubin. RMSD re-docking error was calculated using the program LigRMSD, and the AHR PAS B domain cavity size was calculated using Caver Web 1.0 [26 (link),27 (link)].