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@ARTICLE{LeguizamonHerrera:917333,
author = {Leguizamon Herrera, Vivian Lorena and Buell, Alexander K.
and Willbold, Dieter and Barz, Bogdan},
title = {{I}nteraction of {T}herapeutic d -{P}eptides with {A}β42
{M}onomers, {T}hermodynamics, and {B}inding {A}nalysis},
journal = {ACS chemical neuroscience},
volume = {13},
number = {11},
issn = {1948-7193},
address = {Washington, DC},
publisher = {ACS Publ.},
reportid = {FZJ-2023-00561},
pages = {1638 - 1650},
year = {2022},
abstract = {The aggregation of the amyloid-β (Aβ) peptide is a major
hallmark of Alzheimer’s disease. This peptide can
aggregate into oligomers, proto-fibrils, and mature fibrils,
which eventually assemble into amyloid plaques. The peptide
monomers are the smallest assembly units and play an
important role in most of the individual processes involved
in amyloid fibril formation, such as primary and secondary
nucleation and elongation. Several d-peptides have been
confirmed as promising candidates to inhibit the aggregation
of Aβ into toxic oligomers and fibrils by specifically
interacting with monomeric species. In this work, we
elucidate the structural interaction and thermodynamics of
binding between three d-peptides (D3, ANK6, and RD2) and
Aβ42 monomers by means of enhanced molecular dynamics
simulations. Our study derives thermodynamic energies in
good agreement with experimental values and suggests that
there is an enhanced binding for D3 and ANK6, which leads to
more stable complexes than for RD2. The binding of D3 to
Aβ42 is shown to be weakly exothermic and mainly
entropically driven, whereas the complex formation between
the ANK6 and RD2 with the Aβ42 free monomer is weakly
endothermic. In addition, the changes in the
solvent-accessible surface area and the radius of gyration
support that the binding between Aβ42 and d-peptides is
mainly driven by electrostatic and hydrophobic interactions
and leads to more compact conformations.},
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 = {35580288},
UT = {WOS:000819923000001},
doi = {10.1021/acschemneuro.2c00102},
url = {https://juser.fz-juelich.de/record/917333},
}