Results for an alternative two-replica model is reported in the Supporting Information (Figures S9-S13, Table ). Similar features as for the model discussed here are observed, related the water content and orientation of Loop C. In the case of two consecutive occupation, there seems to be a tendency to have "more closed" pockets, in particular the unoccupied pocket flanked by unoccupied pockets, reminding of the alternation seen in the Apo structure. Across all models, pockets exhibit different levels of water content inside the pocket, Loop orientation, pocket volume (characterized by convex hull volume), and RMSFs. The variance among pockets is primarily due to the action of glycine binding: bound and "more compressed" pockets often show more stability as probed by the MD trajectory analysis, while unbound and "more enlarged" pockets tend to behave in a more unstable manner, subject to increased fluctuations. The presence of the agonist enhance inter-subunits interactions, attracting the principal and complementary subunits, and reducing the space in between. We however observed that an alternation of "compressed" and "expanded" pockets also developed when no ligand is present as in the Apo structure, due to a self-organization and structure optimization of the five subunits, compatible with frustration effects due to the odd subunit number.