Structural, thermodynamical, and dynamical properties of oligomers formed by the amyloid NNQQ peptide: insights from coarse-grained simulations.
Characterizing the early formed oligomeric intermediates of amyloid peptides is of particular interest due to their links with neurodegenerative diseases. Here we study the NNQQ peptide, known to display parallel β-strands in amyloid fibrils by x-ray microcrystallography, and investigate the structural, thermodynamical, and dynamical properties of 20 NNQQ peptides using molecular dynamics and replica exchange molecular dynamics simulations coupled to a coarse-grained force field. All simulations are initiated from randomized and fully dispersed monomeric conformations. Our simulations reveal that the phase transition is characterized by a change in the oligomer and β-sheet size distributions and the percentage of mixed parallel/antiparallel β-strands when the sheets are formed. At all temperatures, however, the fraction of parallel β-strands remains low, though there are many association/fragmentation events. This work and a growing body of computational studies provide strong evidence that the critical nucleus goes beyond 20 chains and reordering of the β-strands occurs in larger oligomers.
State Key Laboratory of Surface Physics, and Department of Physics, Fudan University, 220 Handan Road, Shanghai 200433, China.
Yan
Y
Lu
Guanghong
G
Wei
Philippe
P
Derreumaux
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013696:Temperature; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D016229:Amyloid beta-Peptides; D009842:Oligopeptides; D014867:Water