Helix-coil transition and conformational deformity in Aβ42-monomer: a case study using the Zn2+ cation.

The metal ions (like Fe2+, Zn2+, Cu2+) 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 Zn2+ ion using all-atom molecular dynamics (MD) simulations using explicit solvent models. We have probed the unfolding of the full-length Aβ42 monomer both inclusive and exclusive of the Zn2+ cation, with 1:1 ratio of the peptide and the Zn2+ cation. The inclusion of the Zn2+ cation shows differential intra-peptide interactions which has been probed using various analyses. The Helix - Coil transition of the wild type Aβ42 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 Zn2+ cation. This accounts for the structural and the dynamical variations that take place in the Aβ monomer in the presence of the Zn2+ cation to mimic the conditions/environment at the onset of fibrillation.Communicated by Ramaswamy H. Sarma.