The average numbers of water molecule in the (bound and unbound) pockets are shown in Figure ). In the full-ligand model, pocket (a) includes a slightly higher average number of water molecules, with a value of 1.4 and a significant standard deviation. This is linked to the fact that glycine in pocket (a) became more loosely bound toward the end of the MD, with a significant increase in the water number (as evident in the time-evolution of the water number in the Supporting Information, Figure ). Interestingly, in the Apo structures, the average number of water molecules is higher in the three pockets (a), (c) and (e) at 12.1, 14.6 and 10.1 respectively and significantly lower in (b) and (d) at 5.0 and 6.0 respectively, showing a tendency to have two non-adjacent pockets more contracted even in absence of ligands; this is evidenced also by the "convex hull" volume used to identify the water within the binding pockets in Figure iii). Somehow, this self-organization resembles the case of the two-ligand models, if we consider the space occupied by glycine (roughly equivalent to 4-6 water molecules) as observed in Figure i), suggesting a natural tendency to a favourable assembly where two out of the five binding pockets are more contracted than the others, helped or not by the presence of glycines.