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@ARTICLE{Strodel:134967,
author = {Strodel, Birgit and Whittleston, Chris S and Wales, David
J},
title = {{T}hermodynamics and kinetics of aggregation for the
{GNNQQNY} peptide.},
journal = {Journal of the American Chemical Society},
volume = {129},
number = {51},
issn = {1520-5126},
address = {Washington, DC},
publisher = {American Chemical Society},
reportid = {FZJ-2013-02982},
pages = {16005 - 16014},
year = {2007},
abstract = {The energy landscape of the monomer and dimer are explored
for the amyloidogenic heptapeptide GNNQQNY from the
N-terminal prion-determining domain of the yeast protein
Sup35. The peptide is modeled by a united-atom potential and
an implicit solvent representation. Replica exchange
molecular dynamics is used to explore the conformational
space, and discrete path sampling is employed to investigate
the pathways that interconvert the most populated minima on
the free energy surfaces. For the monomer, we find a rapid
fluctuation between four different conformations, where a
geometry intermediate between compact and extended
structures is the most thermodynamically favorable. The
GNNQQNY dimer forms three stable sheet structures, namely
in-register parallel, off-register parallel, and
antiparallel. The antiparallel dimer is stabilized by strong
electrostatic interactions resulting from interpeptide
hydrogen bonds, which restrict its conformational
flexibility. The in-register parallel dimer, which is close
to the amyloid beta-sheet structure, has fewer interpeptide
hydrogen bonds, making hydrophobic interactions more
important and increasing the conformational entropy compared
to the antiparallel sheet. The estimated two-state rate
constants indicate that the formation of dimers from
monomers is fast and that the dimers are kinetically stable
against dissociation at room temperature. Interconversions
between the different dimers are feasible processes and are
more likely than dissociation.},
keywords = {Oligopeptides (NLM Chemicals)},
cin = {ICS-6},
ddc = {540},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {452 - Structural Biology (POF2-452)},
pid = {G:(DE-HGF)POF2-452},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:18052168},
UT = {WOS:000251974000051},
doi = {10.1021/ja075346p},
url = {https://juser.fz-juelich.de/record/134967},
}