Insights into the misfolding of ‒synuclein in the presence of metal ions: a simulation study

Molecular dynamics of α-synuclein in the presence of five different salt concentrations show that Zn 2+ enhanced the stability of the protein monomer while K + shows opposite effect.Higher regions of α-synuclein unfolding was seen between the residues 100-140 in the presence of NaCl and KCl while the presence of CaCl 2 and MgCl 2 results in similar unfolding between the residues 60-80.In contrast, the unfolding of α-synuclein in the presence of ZnCl 2 deviate from other salts indicating the influence of Zn 2+ in the unfolding of the secondary and tertiary structures of α-synuclein.In protein dimers, these misfolding of α-synuclein are commonly seen between the residues 80-100 in all these five salts indicating that the NAC region of the dimer is mainly involved in protein unfolding.Mutation of Ala30Pro clearly shows that decreased the stability of α-synuclein monomer while Ca 2+ influenced protein aggregation in protein dimer.Removing the residues from 110-140 reduced the stability of monomer in the presence of K + while shows higher stability with Ca 2+ in the protein dimer.However, both Na + and Miens show variations in different forms of the protein.These results show that α-synuclein is less prone to aggregation in the presence of Zn 2+ which may have implications for the prevention and therapeutics of the Parkinson's disease.