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@ARTICLE{Schffler:1033638,
author = {Schäffler, Moritz and Wales, David J. and Strodel, Birgit},
title = {{T}he energy landscape of {A}β 42 : a funnel to disorder
for the monomer becomes a folding funnel for self-assembly},
journal = {Chemical communications},
volume = {60},
number = {92},
issn = {0022-4936},
address = {Cambridge},
publisher = {Soc.},
reportid = {FZJ-2024-06510},
pages = {13574 - 13577},
year = {2024},
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.},
cin = {IBI-7},
ddc = {540},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524)},
pid = {G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)16},
pubmed = {39479923},
UT = {WOS:001345083500001},
doi = {10.1039/D4CC02856B},
url = {https://juser.fz-juelich.de/record/1033638},
}