Helix-coil transition and conformational deformity in Aβ 42-monomer: a case study using the Zn2+ cation

Abstract

The metal ions (like Fe Zn2+, Cu) are known to influence the amyloid beta (Aβ) aggregation. In this study, we have examined the conformational and dynamical changes during the coordination of Aβ-monomer with the Zn ion using all-atom molecular dynamics (MD) simulations using explicit solvent models. We have probed the unfolding of the full-length Aβ 42 monomer both inclusive and exclusive of the Zn cation, with 1:1 ratio of the peptide and the Zn cation. The inclusion of the Zn cation shows differential intra-peptide interactions which has been probed using various analyses. The Helix – Coil transition of the wild type A monomer is studied using the steered molecular dynamics simulations by taking the end-to-end C-α distance across the peptide. This gives an idea of the unequal intra – peptide and peptide – water interactions being found across the length of the Aβ monomer. The transition of an α-helix dominated wild-type (WT) Aβ structure to the unfolded coil structure gives significant evidence of the intra-peptide hydrogen bonding shifts in the presence of the Zn cation. This accounts for the structural and the dynamical variations that take place in the Aβ monomer in the presence of the Zn cation to mimic the conditions/environment at the onset of fibrillation. Communicated by Ramaswamy H. Sarma