a multiscale approach to characterize the early aggregation steps of the amyloid-forming peptide gnnqqny from the yeast prion sup-35多尺度方法描述的早期聚合步骤amyloid-forming肽酵母朊病毒sup-35 gnnqqny.pdfVIP
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a multiscale approach to characterize the early aggregation steps of the amyloid-forming peptide gnnqqny from the yeast prion sup-35多尺度方法描述的早期聚合步骤amyloid-forming肽酵母朊病毒sup-35 gnnqqny
A Multiscale Approach to Characterize the Early
Aggregation Steps of the Amyloid-Forming Peptide
GNNQQNY from the Yeast Prion Sup-35
1 2 3 2
Jessica Nasica-Labouze , Massimiliano Meli , Philippe Derreumaux , Giorgio Colombo *, Normand
Mousseau1*
´ ´ ´ ´ ´
1 Departement de Physique and GEPROM, Universite de Montreal, Montreal, Quebec, Canada, 2 Istituto di Chimica del Riconoscimento Molecolare, CNR, Milano, Italy,
´ ´
3 Laboratoire de Biochimie Theorique, UPR9080 CNRS, Institut de Biologie Physico-Chimique, Universite Paris 7, and Institut Universitaire de France, Paris, France
Abstract
The self-organization of peptides into amyloidogenic oligomers is one of the key events for a wide range of molecular and
degenerative diseases. Atomic-resolution characterization of the mechanisms responsible for the aggregation process and
the resulting structures is thus a necessary step to improve our understanding of the determinants of these pathologies. To
address this issue, we combine the accelerated sampling properties of replica exchange molecular dynamics simulations
based on the OPEP coarse-grained potential with the atomic resolution description of interactions provided by all-atom MD
simulations, and investigate the oligomerization process of the GNNQQNY for three system sizes: 3-mers, 12-mers and 20-
mers. Results for our integrated simulations show a rich variety of structural arrangements for aggregates of all sizes.
Elongated fibril-like structures can form transiently in the 20-
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