Ligand-Induced Modulation of the Free-Energy Landscape of G Protein-Coupled Receptors Explored by Adaptive Biasing Techniques
Figure 4
Simulation results for B2AR bound to the full agonist epinephrine, the very weak partial agonist catechol, and the weak partial agonist dopamine.
(A, D, and G) Free-energy profiles as a function of the position (s) along the activation pathway for epinephrine, catechol, and dopamine, respectively. Note that the curves have been shifted so that the minima (indicated by stars) correspond to reference free-energy values. (B, E, and H) Binding modes of epinephrine, catechol, and dopamine, respectively. Relevant residues interacting with the ligands (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, F, and I) Free-energies as a function of ionic lock distance (dIL) and the toggle switch dihedral (χTS) molecular switches for the epinephrine-, catechol-, and dopamine-bound B2AR, respectively.