Fig. 5.

2D potential of mean force (PMF) or free energy profiles (in kcal/mol) based on G_sα conformation and its possible partial dissociation from β₂AR based on all-atom Anton MD simulations of the active state of the human β₂AR–G_s complexes with NE(+). The 0.5 kcal/mol contour lines are shown as bold black curves. Relative free energy values from 0 to 8 kcal/mol are indicated by different colors from blue to red. All distances were measured between geometric centers of protein residues or domains. (A) A161–E299 distance indicating G_sα opening or closing is shown as X-axis; distance between G_sα α5 and β₂AR indicating possible partial G_s dissociation is shown as Y-axis. (B) G_sα α1–α5 distance is shown as X-axis; distance between G_sα α5 and β₂AR is shown as Y-axis. The contour lines are smoothed for better visualization.