Byline: Bin Zhang, Chuan-dong Fang, Jun-hui Xu, Hui-juan Cao Keywords: cadmium (Cd.sub.2+); depuration; hydrolysate-Fe.sub.2+ (PH-Fe.sub.2+); metallothionein (MT); Mytilus edulis Abstract Metallothionein (MT) plays a major role in the detoxification of toxic metal ions in mussel. This study served to investigate the effects of prepared protein hydrolysate-Fe.sub.2+ (PH-Fe.sub.2+) on depuration of cadmium salt (Cd.sub.2+) from blue mussel (Mytilus edulis). The results indicated that Cd.sub.2+ concentrations in control ranged from 46.1 to 47.1 AaAaAeAA1/4g/g during 15 d of depuration. While, 40 mg/L PH-Fe.sub. feed mussels exhibited obvious changes in Cd.sub.2+ concentration variables, which decreased by 22.8 AaAaAeAA1/4g/g after 15 d of depuration, making th significantly lower than the values of the control. Our assumption was that Cd.sub.2+ could be dissociated effectively from the complex of MT-Cd.sub.2+ in mussels affected by the incorporation of PH-Fe.sub.2+ during the feeding period. Further results of homology modeling and molecular dynamics (MD) confirmed that the combined power between MT and Cd.sub.2+ weakened significantly by PH-Fe.sub.2+. This condition affected the charge density and/or the loop flexibility of MT and decreased the interaction energy within MT-Cd.sub.2+ complex and resulted in the release of Cd.sub.2+ from the complex, thereby exhibiting excretion detoxification. Finally, by comparing the experimental results to MD results, significant positive correlations were observed between PH-Fe.sub.2+ and the depuration of Cd.sub.2+ from MT-Cd.sub.2+ complex. Overall, the findings of this study may help better understand the depuration mechanisms of Cd.sub.2+ combined with MT, and the PH-Fe.sub.2+ can be recommended as a depuration agent to decrease Cd.sub.2+ concentrations in mussels. Practical Application Metallothionein (MT) is a low-molecular-weight protein with high metal-ion affinity. If the intracellular concentrations of metals are too high or if toxic metals are present within the cell, then the synthesis of MTs is induced and generated. In our previous work, it was found that the prepared hydrolysate-metal element complex showed obvious depuration activity of heavy metals (Cd.sub.2+) from blue mussel (Mytilus edulis). This study provided further the depuration mechanisms of Cd.sub.2+ from mussel (M. edulis), in particular to the role of MT and its chelate during the depuration process.