Figure 6.

Metoprolol induces a conformational change in the human β1AR that increases the size of the intracellular cavity. (A) Modelling of the human β1AR modelling alone (grey) and bound to epinephrine (purple), metoprolol (blue), atenolol (orange), or propranolol (green). Each ligand-bound β1AR conformation was compared to the unbound β1AR conformation. Images were obtained with the PyMOL molecular visualization system. In silico analysis indicates that β1AR conformational changes induced by metoprolol binding differ from those induced by the other ligands, producing an enlarged intracellular receptor cavity that is more open than that of the epinephrine-, atenolol-, or propranolol-bound receptor. (B) Superposition of all β-blocker-induced β1AR conformations. The energies of the complex and interface are shown in Rosetta Energy Internal Units, whereas cavity sizes are shown in square Ångström Units (Ų).