Journal Article

FZJ-2013-02982

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Thermodynamics and kinetics of aggregation for the GNNQQNY peptide.

Strodel, B. (Corresponding author)FZJ* ; Whittleston, C. S. ; Wales, D. J.

2007
American Chemical Society Washington, DC

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Please use a persistent id in citations: doi:10.1021/ja075346p

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.

Keyword(s): Oligopeptides

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Contributing Institute(s):

1. Strukturbiochemie (ICS-6)

Research Program(s):

1. 452 - Structural Biology (POF2-452) (POF2-452)

Appears in the scientific report 2013

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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