Fig. 1.

Molecular dynamics simulations identified intermediate conformational states. (A) Climber Energy (kcal/mol) (blue line) and RMSD with respect to inactive (red dashed line) and active (red dash-dotted line) conformations (PDBIDs: 5X7D and 3SN6, respectively) during the morphing from the active to inactive form of β2AR. Black dots display the local energy minima along the morphing pathway selected for the two starting intermediate conformations. (B–E) Ionic-lock distance analysis from the MD simulations. (B and C) Time evolution of the ionic-lock distance from the MD simulations in the presence of BI-167107 or Carazolol, respectively. Green vertical dashed lines represent the ionic-lock alpha carbon distance measured from the inactive (~11 Å) and active (~19.5 Å) receptor. (D and E) Density distributions of the ionic-lock distance from the MD simulations in the presence of BI-167107 or Carazolol, respectively. The simulations in B and C were initiated from the Step74 conformation.