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@ARTICLE{Samantray:889721,
author = {Samantray, Suman and Yin, Feng and Kav, Batuhan and
Strodel, Birgit},
title = {{D}ifferent {F}orce {F}ields {G}ive {R}ise to {D}ifferent
{A}myloid {A}ggregation {P}athways in {M}olecular {D}ynamics
{S}imulations},
journal = {Journal of chemical information and modeling},
volume = {60},
number = {12},
issn = {1549-960X},
address = {Washington, DC},
publisher = {American Chemical Society64160},
reportid = {FZJ-2021-00343},
pages = {6462 - 6475},
year = {2020},
abstract = {The progress toward understanding the molecularbasis of
Alzheimers’s disease is strongly connected to
elucidatingthe early aggregation events of the amyloid-β
(Aβ) peptide.Molecular dynamics (MD) simulations provide a
viable techniqueto study the aggregation of Aβ into
oligomers with high spatial andtemporal resolution. However,
the results of an MD simulation canonly be as good as the
underlying force field. A recent study by ourgroup showed
that none of the common force fields can distinguishbetween
aggregation-prone and nonaggregating peptide sequences,
producing a similar and in most cases too fast
aggregationkinetics for all peptides. Since then, new force
fields specially designed for intrinsically disordered
proteins such as Aβ weredeveloped. Here, we assess the
applicability of these new force fields to studying peptide
aggregation using the Aβ16−22 peptide andmutations of it
as test case. We investigate their performance in modeling
the monomeric state, the aggregation into oligomers, andthe
stability of the aggregation end product, i.e., the
fibrillar state. A main finding is that changing the force
field has a stronger effecton the simulated aggregation
pathway than changing the peptide sequence. Also the new
force fields are not able to reproduce theexperimental
aggregation propensity order of the peptides. Dissecting the
various energy contributions shows that
AMBER99SB-dispoverestimates the interactions between the
peptides and water, thereby inhibiting peptide aggregation.
More promising results areobtained with CHARMM36m and
especially its version with increased protein−water
interactions. It is thus recommended to usethis force field
for peptide aggregation simulations and base future
reparameterizations on it.},
cin = {IBI-7},
ddc = {540},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
pubmed = {33174726},
UT = {WOS:000608875100080},
doi = {10.1021/acs.jcim.0c01063},
url = {https://juser.fz-juelich.de/record/889721},
}