TY  - JOUR
AU  - Schäffler, Moritz
AU  - Wales, David J.
AU  - Strodel, Birgit
TI  - The energy landscape of Aβ 42 : a funnel to disorder for the monomer becomes a folding funnel for self-assembly
JO  - Chemical communications
VL  - 60
IS  - 92
SN  - 0022-4936
CY  - Cambridge
PB  - Soc.
M1  - FZJ-2024-06510
SP  - 13574 - 13577
PY  - 2024
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 39479923
UR  - <Go to ISI:>//WOS:001345083500001
DO  - DOI:10.1039/D4CC02856B
UR  - https://juser.fz-juelich.de/record/1033638
ER  -