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 peptide 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.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call