Molecular docking was carried out using Glide program57 (link),58 (link),66 included in Maestro 9v0.73 Glide uses a hierarchical series of filters to search for possible locations of the ligand in the active-site region of the receptor. The shape and properties of the receptor are represented on a grid by several different sets of fields that provide progressively more accurate scoring of the ligand poses. Ligand conformational flexibility is handled in Glide by an extensive conformational search, augmented by a heuristic screen that rapidly eliminates unsuitable conformations. The final scoring of the poses is carried out using Schrödinger’s proprietary GlideScore multi-ligand scoring function.
Grids for mAhR homology models were set up using default parameters. The binding box was centered in the averaged X, Y, Z coordinates of the three THS ligands centroids with 12 Å sides length. Flexible ligand docking was carried out in standard precision (SP) approach saving only one final pose. All the other parameters are the default ones.
The rescoring of the energy minimized complexes was performed using Glide extra precision (XP) scoring function.53 (link) All the other parameters are the default ones.
The rescoring of the PCDD docking poses into the rtAhR model was performed by molecular mechanics generalized Born/surface area (MM-GBSA), which uses MD simulations of the free ligand, free protein, and their complex as a basis for calculating the binding free energy of protein-ligand complexes. This calculation was performed using Prime MM-GBSA,67 excluding entropic terms, with a flexible receptor shell within 8 Å from the ligand.
Grids for mAhR homology models were set up using default parameters. The binding box was centered in the averaged X, Y, Z coordinates of the three THS ligands centroids with 12 Å sides length. Flexible ligand docking was carried out in standard precision (SP) approach saving only one final pose. All the other parameters are the default ones.
The rescoring of the energy minimized complexes was performed using Glide extra precision (XP) scoring function.53 (link) All the other parameters are the default ones.
The rescoring of the PCDD docking poses into the rtAhR model was performed by molecular mechanics generalized Born/surface area (MM-GBSA), which uses MD simulations of the free ligand, free protein, and their complex as a basis for calculating the binding free energy of protein-ligand complexes. This calculation was performed using Prime MM-GBSA,67 excluding entropic terms, with a flexible receptor shell within 8 Å from the ligand.
