Ligand-Induced Modulation of the Free-Energy Landscape of G Protein-Coupled Receptors Explored by Adaptive Biasing Techniques
Figure 2
Simulation results for B2AR bound to the neutral antagonist alprenolol.
(A) Free-energy profile as a function of the position (s) along the activation pathway. Note that the curve has been shifted so that the minimum (indicated by a star) corresponds to a reference free-energy value. (B) Binding mode of alprenolol. Relevant residues interacting with the ligand (any atom within a 3 Å distance cutoff) are indicated in stick representations. Helices TM5, TM6 and TM7 are shown in orange, blue and light blue respectively. Helix TM3 is shown in purple transparent representation whereas TM4 has been removed for clarity. (C) Free-energy as a function of ionic lock distance (dIL) and the toggle switch dihedral (χTS) molecular switches.