Effect of Piedmont mutation (L34V) on the structure, dynamics, and aggregation of Alzheimer's Aβ40 peptide.

Journal of Molecular Graphics & Modelling
Rajneet Kaur SainiBhupesh Goyal

Abstract

The amyloid-β (Aβ) aggregation in the brain has been associated with the development of Alzheimer's disease (AD). The previous studies have reported that Piedmont mutation (L34V) increases the rate of Aβ40 aggregation. However, the underlying molecular mechanism of the effect of L34V mutation on Aβ40 structure, dynamics, and aggregation remains largely unclear. In the present study, molecular dynamics (MD) simulations were performed to elucidate the effect of L34V mutation on the structural changes and conformational dynamics of Aβ40. The secondary structure analysis highlight that L34V mutation enhances Aβ40 self-assembly due to the formation of aggregation-prone β-sheet structure at the C-terminus of Aβ40 monomeric structure. The higher probability of Asp23-Lys28 salt bridge interaction in Aβ40(L34V) leads to aggregation prone β-sheet conformations, which has the potential to increase the fibril formation rate. The free energy landscape (FEL) analysis depict a sampling of coil conformation in the free energy minima of Aβ40, whereas the aggregation-prone β-sheet conformation was observed at the C-terminal region of Aβ40(L34V) in the minimum energy conformations extracted from FEL of Aβ40(L34V). MD simulations, in agreement wit...Continue Reading

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Sep 29, 2020·International Journal of Nanomedicine·Ehsan AlimohammadiMilad Rezaian
Apr 24, 2021·Journal of Materials Science. Materials in Medicine·Ahmad Miri JahromiLobat Tayebi

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