Molecular mechanism of the effect of ZnCl2 and MgCl2 solution on the conformation of the tau267–312 monomer

Alzheimer's disease is generally believed to be caused by abnormal aggregation of tau protein; however, there remains a lack of understanding about the aggregation process of tau protein in a solution environment. To explore the conformational properties of the tau protein monomer (tau_267-312) in the presence of zinc and magnesium ions, we performed all-atom molecular dynamics simulations of tau_267-312 in solutions of zinc chloride and magnesium chloride at different concentrations and compared these results with those obtained in pure water. The calculation results show that the β-sheet content increases significantly in the presence of zinc and magnesium ions, which causes a more compact structure for the tau protein monomers. Furthermore, it was found that stronger interactions between residues, as well as alterations in hydrophilic and hydrophobic interactions, are molecular mechanisms driving structural changes within the tau protein monomers. These findings suggest that zinc and magnesium ions facilitate a more stable conformation and promote the aggregation of tau protein monomers, which is important for understanding the aggregation and folding process of tau protein in the environment of saline solution.