A Multiscale Approach to Characterize the Early Aggregation Steps of the Amyloid-Forming Peptide GNNQQNY from the Yeast Prion Sup-35

• DOI: 10.1371/journal.pcbi.1002051
• Publication Date: 2011-05-19T20:49:20Z
• Authors: Jessica Nasica-La...; Massimiliano Meli; Philippe Derreumaux; Giorgio Colombo; Normand Mousseau
• Keywords: Characterization; Amyloid (mycology); Sequence (biology)

The self-organization of peptides into amyloidogenic oligomers is one the key events for a wide range molecular and degenerative diseases. Atomic-resolution characterization mechanisms responsible aggregation process resulting structures thus necessary step to improve our understanding determinants these pathologies. To address this issue, we combine accelerated sampling properties replica exchange dynamics simulations based on OPEP coarse-grained potential with atomic resolution description interactions provided by all-atom MD simulations, investigate oligomerization GNNQQNY three system sizes: 3-mers, 12-mers 20-mers. Results integrated show rich variety structural arrangements aggregates all sizes. Elongated fibril-like can form transiently in 20-mer case, but they are not stable easily interconvert more globular disordered forms. Our extensive intermediate their physico-chemical points high degree polymorphism sequence that be reflected at macroscopic scale. Detailed underlie amyloid also provided.