The zwitterionic glycine acts as a bridge across adjacent subunits by interacting with the side chains of two residues with opposite charge: GLU173 (Loop B) and ARG81 (Loop D) through its charged groups. In our MD simulations, while glycine displays persistent interactions with the positively charged ARG81 via its carboxylate group to form a saltbridge (often with two bonds as shown in Figure i), it does not interact directly with the negatively charged GLU173 through its amino group, but forms a water bridge with it which helps stabilize its binding. Other persistent direct hydrogen bonds are formed with SER145 (Loop E), THR220 (at the apex of Loop C, effectively locking such a loop over the binding pocket) and PHE175 (Loop B), which also plays an important role in cation-π interactions. Besides GLU173, SER174 in Loop B predominantly participates in a water bridge, involving the same water molecule, with glycine, as shown in Figure ). This is consistent with previous MD 55, and structural imaging 57 work. However, an increase in the amount of water in the binding pocket may disturb, rather than enhance, the interactions between the ligand and the binding residues; in some of the binding pockets several other water-bridged interactions occur, in some cases short lived. Hence examining the amount of water molecules in the binding pockets provides useful indications on the binding stability of the ligand.