Effect of Ala-substitution, N- and C-terminal modification and the presence of counter ions on the structure of amyloid peptide fragment 25-35

The effect of the Ala-substitution, the N- and C-terminal capping and the presence of Ca²⁺, Mg²⁺ and Zn²⁺ on the structure of amyloid peptide fragment, Aβ(25-35), and its analog, [Ala^31,32,34,35]Aβ(25-35), was studied. One nanosecond NPT molecular dynamics simulation was used to examine the structural stability of the peptides in water. Calculations were performed using the modified GROMOS-87 force field with SPC/E water model, applying the weak temperature and pressure coupling method. During the simulation of the Aβ(25-35) structure, an initial helical structure was destroyed. In Ac-[Ala^31,32,34,35]Aβ(25-35)-NHCH₃, however, the helix was stable and even more so in the presence of Ca²⁺, Mg²⁺ and Zn²⁺ cations. Between residues 27 and 34, mainly turn/bend and less frequently helix, respectively, characterized the secondary structure of Aβ(25-35) and [Ala^31,32,34,35]Aβ(25-35).