The inter-subunit interactions were further analyzed using a protein distance contact map, as shown in Figure and S8 in the Supporting Information. Two distinct regions, labelled "Region 1" and "Region 2" in Figure , display notable differences between bound and unbound pockets and across bound models versus the zero-ligand model. "Region 1" reflects interactions between Loop C of the principal subunit and residues on the complementary subunit, with weakened interactions in unbound pockets. Focusing specifically on the interactions between Loop C on the principal subunit and Loop F on the complementary subunit, Figure reveals that unbound or "more enlarged" pockets typically exhibit weakened interactions between (+, Loop C)ASN219 and (-, Loop F)LYS189, while bound or "more compressed" pockets tend to show enhanced interactions at this site. In the zeroligand model, potential interactions in "Region 2" are absent due to the tilting of the subunit in the Apo state.