PROMISCUOUS LIGANDS AND ATTRACTIVE CAVITIES

Cartoon of a protein (green circles) conformational ensemble with hypothetical free-energy curves depicted underneath. A. The middle conformation has an enlarged internal cavity, at the expense of a higher free energy, and is therefore poorly populated at equilibrium as shown by the size of the arrows.B. The addition of an anesthetic (red ovals) that binds to the cavity preferentially stabilizes and favors the central conformer. Whatever activity is associated with this conformer (e.g., activation of chloride channels) would therefore be enhanced by the anesthetic.