Molecular mechanism of the effect of ZnCl2 and MgCl2 solution on the conformation of Tau267-312 monomer

Abstract

Alzheimer’s disease is generally believed to be caused by abnormal aggregation of tau protein, however, it remains scarce that people’s understanding of the aggregation process of tau protein in solvent environment. To explore the conformational properties of the tau protein monomer (tau267−312) in the presence of zinc and magnesium ions, we performed all-atom molecular dynamics simulations of tau267−312 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 content of β-sheet increases significantly in the presence of zinc and magnesium ions, which just 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 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.