Figure 11.

Environment and interactions of the bound ligands. (A) The environment of the ligand-binding cavity is shown for the equilibrated agonist^MD model (at 50 ns) colored by atom: carbon, grey; oxygen, red; nitrogen, blue; sulfur, yellow. TCDD is depicted with sticks (with carbon atoms colored in cyan); active site residues that form transient hydrogen bonds with the buried polar groups of the ligand are noted with (*). The important interacting residues of the bound TCDD are shown, and residues which have been investigated via mutagenesis and found to influence TCDD binding are noted in black boxes [13,18]. (B) As in panel A, the active site cavity is shown for the equilibrated antagonist^MD model (at 50 ns). (C) Residues contacting the ligand (within 4 Å) during the final 10 ns of simulation are shown with the percentage of contact time noted for agonist^MD (blue) and antagonist^MD (orange). For those with less than 90% contact time over the final 10 ns, we note whether this is due to fluctuation from being on the pocket boundary (denoted with “B”) or due to a conformational shift (denoted with “C”), for which we also note the time of occurrence. (D) Shown is a plot of root mean square fluctuation of Cα atoms to illustrate structural dynamics for apo^MD (solid green) agonist^MD (solid cyan), antagonist^MD (solid orange) as calculated by VMD [33] during the last 5 ns of simulation. The Cα shifts between apo^MD and agonist^MD (dashed cyan) and between apo^MD and antagonist^MD (dashed orange) are also shown on the same scale, but for clarity their values are adjusted +20 Å. The 307–329 segment is highlighted in gold, with the secondary structure of the apo^MD given for reference, and the regions interacting with HSP90 in the murine system are noted by the black bar.