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 beta-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 beta-sheet size distributions and the percentage of mixed parallel/antiparallel beta-strands when the sheets are formed. At all temperatures, however, the fraction of parallel beta-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 beta-strands occurs in larger oligomers. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4732761]