Figure 3.

Keeping the conformation of a region of the 7TMR relatively fixed (through binding of a ligand) will lead to a biased ensemble of conformations throughout the protein. Insofar as some of those are associated with coupling to cellular signalling proteins, this will define the pharmacologic action of the ligand when the receptor is in the cell membrane. These various signalling regions of the receptor will adopt an ‘active state’ conformation with a range of probabilities depending on the nature of the ligand (histogram in panel B). Specifically, the frequency of occurrence of any given conformation will be influenced by the nature of the ligand binding to the receptor leading to a unique frequency distribution of conformations associated with that ligand.