Investigation of dihedral angles and hydrogen-bond networks within the ligand binding pocket of the simulation systems.

<p>(A) Ligand-specific regulation of the dihedral angle of residue His393^6.55 (atoms: C-Cα-Cβ-Cγ), depicted as red, grey and blue lines for the dopamine-, the aripiprazole- and the FAUC350-complexes, respectively. (B) The dihedral angle of residue Ser194^5.43 (atoms: C-Cα-Cβ-Cγ) within the dopamine-simulation is shown as red lines. Unlike a constant value observed within the dopamine system, both aripiprazole (left insert) and FAUC350 (right insert) cause a greater flexibility of this dihedral angle. (C) Hydrogen-bond interactions between representative residues of helices TM2, TM3, TM5, TM6 and TM7. Aripiprazole (grey values) and FAUC350 (blue values) cause a ligand-specific modulation within interhelical networks in proximity to the binding pocket compared to dopamine (red values). (D) Representative snapshots of D2R within the dopamine-, the aripiprazole- and the FAUC350-complexes shown as red, grey and blue ribbons, respectively. The snapshots represent average structures taken from 950–975 ns (dopamine), 750–775 ns (aripiprazole) and 350–375 ns (FAUC350). The superposition of these structures visualizes ligand-specific changes within interhelical networks in proximity to the binding pocket. Helix movements are indicated with green arrows.