Metallothionein (MT) is a low-molecular-weight protein with high metal-ion affinity,which plays a major role in the metabolism of metal ions in mussel.This study served to investigate the effects of prepared protein hydrolysate-Fe2+ (PH-Fe2+) on the depuration of cadmium salt (Cd2+) from blue mussel (Mytilus edulis) and focused primarily on the role of MT and MT-Cd2+ during the depuration process on the basis of molecular dynamics (MD) simulation analysis.The results indicated that Cd2+ concentrations in mussels were 46.125-47.118 μg/g after 5 d of exposure to 0.32 mg/L Cd2+ in seawater.Next,40 mg/L PH-Fe2+ feed mussels showed obvious changes in Cd2+ concentration variables,which decreased by 22.878 μg/g after 15 d of depuration,making them significantly lower than the values of the control,the PH,the FeCl2,and the PH + FeC12 treatments.Our assumption was that Cd2+ could be dissociated effectively from the complex of MT-Cd2+ affected by the incorporation of PH-Fe2+.Further results of homology modeling and MD simulations confirmed that the combined power between MT and Cd2+ weakened significantly (P < 0.05) by PH-Fe2+.This condition affected the charge density and/or the loop flexibility of MT and also decreased the interaction energy within the MT-Cd2+ complex and resulted in the release of Cd2+ from the complex,thereby limiting Cd2+-induced toxicity and exhibiting excretion detoxification.Finally,by comparing the experimental results to the MD simulation results,significant positive correlations were observed between PH-Fe2+ and the depuration of Cd2+ from the MT-Cd2+ complex.This study could prove helpful in understanding the depuration mechanisms of heavy metals from mussel,and meanwhile,PH-Fe2+ can be recommended as a depuration agent in mussel feed to decrease Cd2+ concentrations in tissues.