Molecular dynamics study of conformation transition from helix to sheet
of Aβ42 peptides
Abstract
Aβ42 peptides can form helix and sheet structure under different
conditions. The conformational conversion is closely associated with Aβ
peptides aggregation and their neurotoxicity. But the transition from
helix to sheet is not be clearly understood. In this study we performed
microsecond timescale MD simulations of Aβ42 peptides to investigate the
conformation transition from α-helix to β-sheet. Markov state model
(MSM) was built to facilitate identification of crucial intermediate
states and possible transition pathway. Based on the analysis, we found
that the region Y10-A21 in the middle of Aβ42 peptide plays an initial
role in this transition. MSM model revealed that the collapse of helical
structure in this region might trigger the formation of sheet structure.
Moreover, we further simulated the aggregation of Aβ42 peptides with
different conformations. We found that the Aβ42 peptides forming sheet
structure have higher aggregation potential compared with peptides with
helix structure. These results demonstrate that we can prevent the
aggregation of Aβ42 peptides by stabilizing the helix structure in the
region of Y10-A21. In addition, this study provides new insight into
better understanding the conformational transition and aggregation of
Aβ42 peptides.