Paper Info
Title
A Multiscale Approach To Characterize The Early Aggregation Steps Of The Amyloid-Forming Peptide Gnnqqny From The Yeast Prion Sup-35
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-mer case, but they are not stable and easily interconvert in more globular and disordered forms. Our extensive characterization of the intermediate structures and their physicochemical determinants points to a high degree of polymorphism for the GNNQQNY sequence that can be reflected at the macroscopic scale. Detailed mechanisms and structures that underlie amyloid aggregation are also provided.
Year
DOI
Venue
2011
10.1371/journal.pcbi.1002051
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
molecular dynamics simulation,oligopeptides,self organization,polymorphism,protein conformation,amyloid
Biology,Amyloid,Peptide,Yeast,Molecular dynamics,Bioinformatics,Saccharomyces cerevisiae Proteins,Protein structure
Journal
Volume
Issue
ISSN
7
5
1553-7358
Citations 
PageRank 
References 
1
0.43
6
Authors
5
Name
Order
Citations
PageRank
Jessica Nasica-Labouze120.87
Massimiliano Meli210.43
Philippe Derreumaux37014.13
Giorgio Colombo44911.77
Normand Mousseau582.02