Figure 6

(A) All atom per residue RMSD within the TREK1 TM2/TM3 loop from TREK1 wildtype (WT) + Isoflurane Trajectory 1 (black symbols) or Trajectory 2 (gray symbols), as compared with the final frame of the equilibrated TREK1 WT-Free simulation. (B) A representative equilibrium MD simulation snapshot of TREK1 WT. The G182 residue is represented as a sphere and the pi-stacking interaction between F185 and F214 is shown. (C) Side chain χ 1 dihedral angle residence plots for residue F185 and F214 during the TREK1 WT-free (top) and TREK1 WT + isoflurane simulation trajectories (middle, bottom) (D) Pi-stacking plots for the F185/F214 residue interaction, examined by sampling the average number of pi-stacked snapshots over a rolling window of 10 snapshots spanning every 200 fs across the entire simulation timescale. The red bar in the TREK1 WT + Isoflurane trajectory one panel represents the time when isoflurane escaped the binding pocket during this simulation. (E) Representative equilibrium MD simulations snapshots of G182W, showing retained pi-stacking of the F185 and F214 residues or (G,H) simulation snapshots of TREK1 in the presence of isoflurane with disrupted F185/F214 pi-stacking.