The water molecule (or hydroxide) remained coordinated to the zinc throughout the simulation, exhibiting an average bond length of approximately 2 Å in both systems. A significantly elongated bond with a broader distribution of interatomic distances was observed between the metal and the carbonyl oxygen of the scissile peptide bond. The mean distance was marginally greater for oxytocin (3.12 Å) and displayed a larger standard deviation (0.41 Å) than for angiotensin IV (2.81 ± 0.32 Å), indicating increased conformational flexibility of oxytocin (Figure and Figure of the SI). These extended distances suggest that the peptides do not interact with zinc via direct coordination bonds but rather through weak attractive non-covalent interactions (NCIs) clasified as a spodium bonds (SpBs). This type of interaction, wherein a Lewis base or anion donates a lone pair to the antibonding σ * orbital (sigma hole) of the metal, is prevalent in zinc-containing metalloproteins. The SpB identifyied in IRAP was visualised as a green isosurface between the zinc ion and oxygen of the scissile peptide bond. This interaction was characterised using NCI analysis based on the peaks observed in the reduced density gradient (RDG). The analysis was performed using singlepoint calculations at the B3LYP-D3BJ/6-31G(d)/MM level of theory on representative structures extracted from DFTB3/MM molecular dynamics simulations (Figure and Figure of the SI).