Journal Article

FZJ-2024-06510

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The energy landscape of Aβ 42 : a funnel to disorder for the monomer becomes a folding funnel for self-assembly

Schäffler, M.FZJ* ; Wales, D. J. ; Strodel, B. (Corresponding author)FZJ*

2024
Soc. Cambridge

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Please use a persistent id in citations: doi:10.1039/D4CC02856B  doi:10.34734/FZJ-2024-06510

Abstract: The aggregation of amyloid-β (Aβ) peptides, particularly Aβ1–42, plays a key role in Alzheimer's disease pathogenesis. In this study, we investigate how dimerisation transforms the free energy surface (FES) of the Aβ1–42 monomer when it interacts with another Aβ1–42 peptide. We find that the monomer FES is a structurally inverted funnel with a disordered state at the global minimum. However, in the presence of a second Aβ1–42 peptide, the landscape becomes a folding funnel, leading to a β-hairpin state. Using first passage time analysis, we analyse the pathway for the transition from disordered to the β-hairpin state, which highlights the initial formation of a D23–K28 salt bridge as the driving force, together with hydrophobic contacts.

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Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5244 - Information Processing in Neuronal Networks (POF4-524) (POF4-524)

Appears in the scientific report 2024

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Database coverage:
; ; ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; Index Chemicus ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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