Salts exist in any cell and living organism in contact with biological macromolecules. How these salts affect biomolecules such as enzyme is important from both basic sciences and practical technologies. It was observed that divalent salts can change structure and function of protein at higher concentrations. Here, we investigated the effect of divalent salt on the behavior of a multimeric enzyme. We treated glucose oxidase as dimer-active enzyme in different CaCl2 concentration and seen that the enzyme become inactive at high concentration of salt. These experimental results are in agreement with recently published researches. To find a possible mechanism, a series of molecular dynamics simulation of the enzyme were performed at different salt concentration. According to the MD simulation, the conformational changes at the active site and FAD-binding site support the hypothesis of enzyme inactivation at high CaCl2 concentration. MD simulations also showed that enzyme has an unstable conformation at higher salt concentration which is in agreement with our experimental data. Detailed structural properties of the enzyme have been analyzed under different conditions. To the best of our knowledge, this is the first study that bears detailed structural mechanism about the salt effects on multimeric macromolecules

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