Zinc plays important roles in structural stabilization of proteins, eniyine catalysis, and signal transduction. Many Zn binding sites are located at the interface between the protein and the cellular fluid. In aqueous solutions, Zn ions adopt an octahedral coordination, while in proteins zinc can have different coordinations, with a tetrahedral conformation found most frequently. The dynainics of Zn binding to proteins and the formation of complexes that involve Zn are dictated by interactions between Zn and its binding partners. We calculated the interaction energies between Zn and its ligands in complexes that mimic protein binding sites and in Zn complexes of water and one or two amino acid moieties, using quantum mechanics (QM) and molecular mechanics (MM). It was found that MM calculations that neglect or only approximate polarizability did not reproduce even the relative order of the QM interaction energies in these complexes. Interaction energies calculated with the CHARMM-Diode polarizable force field agreed better with the ab initio results,:although the deviations between QM and MM were still rather large (40-96 kcallmol). In order to gain further insight into Zn ligand interactions, the free energies of interaction were estimated by QM calculations with continuum solvent representation, and we performed energy decomposition analysis calculations to examine the characteristics of the different complexes. The ligand-types were found to have high impact on the relative strength of polarization and electrostatic interactions. Interestingly, ligand ligand interactions did not play a significant role in the binding of Zn. Finally) analysis of ligand exchange energies suggests that carboxylates could be exchanged with water molecules, which explains the flexibility in Zn:binding dynamics. An exchange between earboxylate (Asp/Glii) and imidazole (His) is less likely.