The bottom panels of Fig. visually depict representative snapshots obtained along different regions of the FES. The central structure corresponds to CN ≃ 3.6 (the global minimum of the FES) where only two of the three hydroxamate functional groups of DFO interact with Zr 4+ . This illustrates that the rest of the molecule involving the N-terminus is not involved in the chelation complex. The rightmost structure of Fig. corresponds to CN ≃ 5, with the three hydroxamate groups surrounding the Zr 4+ cation as in the DFT structure. This complex is higher up in free energy. As we will see below, finite temperature alters the conformational fluctuations of the DFO molecule as well as the hydrogen bonds between the hydroxamate groups and the water molecules which in turn affect the binding mechanisms.