Interaction of mancozeb with human hemoglobin: Spectroscopic, molecular docking and molecular dynamic simulation studies

Mancozeb is a broad-spectrum fungicide used extensively in agriculture to protect plants from numerous diseases. Hemolysis of human erythrocytes on exposure to mancozeb has been reported. In the present study, we investigated the interaction of mancozeb with human hemoglobin (Hb) using multi-spectroscopic techniques, molecular docking and molecular dynamic simulation. UV-visible spectroscopy studies suggested intimate binding of mancozeb to Hb. Mancozeb quenched the intrinsic fluorescence of Hb and Stern-Volmer plots revealed that the quenching mechanism was of static type. Evaluation of thermodynamic parameters indicated that the binding of Hb to mancozeb was spontaneous, with van der Waals forces and hydrogen bonding being the key contributors in the binding reaction. Synchronous fluorescence experiments demonstrated that mancozeb altered the microenvironment around tryptophan residues, whereas polarity around tyrosine residues was not changed. Circular dichroism studies showed a decrease in the alpha helical content of Hb upon interaction with mancozeb. The inhibition of esterase activity showed that mancozeb can impair the enzymatic functions of Hb. Molecular docking study revealed that strong binding affinity existed between mancozeb and Hb, with hydrophobic forces playing a crucial role in the interaction. Molecular dynamic simulation showed that mancozeb formed a stable complex with Hb resulting in slight unfolding of the protein. To sum up, the results of this study show that mancozeb binds strongly to Hb, induces conformational changes in Hb and adversely affects its function.