Fig. 9.

The number of water contacts as a measure of solvation (wetting or hydration) of the ligands (A) and binding site residues (B) during the dissociation of salmeterol, formoterol, and salbutamol. The water contacts were at a minimum at the start of the simulation (t = 0 ns) when the ligands were bound. The contacts increased gradually as the ligands drifted away from the binding site and the degree of increase was directly proportional to the ligand size in the order of salmeterol > formoterol > salbutamol. Notably, the water contacts decreased for salmeterol, indicating its relocation into the surrounding membrane. Similarly, the number of water contacts with the binding site residues increased gradually, converging to approximately the same number of contacts (∼28).