@article{bibcite_534,
  keywords = {Alzheimer Disease, Amyloid beta-Peptides, aggregation, fibril elongation, disorder},
  author = {I. M. Ilie and A. Caflisch},
  title = {Disorder at the tips of a disease-relevant Aβ42 amyloid fibril: A molecular dynamics study},
  abstract = {<p>We present a simulation study of the early events of peptide dissociation from a fibril of the Alzheimer{\textquoteright}s A\&beta;42 peptide. The fibril consists of layers of two adjacent A\&beta;42 peptides each folded in an S-shaped structure which has been determined by solid state NMR spectroscopy of a monomorphic disease-relevant species. Multiple molecular dynamics runs (16 at 310 K and 15 at 370 K) were carried out starting from an 18-peptide protofibril for a cumulative sampling of about 15 \&mu;s. The simulations show structural stability of the fibrillar core and an overall increase in the twist to about 3 degrees. The N-terminal segment 1-14 is disordered in all peptides. At both ends of the fibril, the central segment 21-29, which includes part of the \&beta;<sub>2</sub> strand, dissociates in some of the simulations. The \&beta;<sub>1</sub> and \&beta;<sub>3</sub> strands, residues 15-20 and 35-41, respectively, are structurally stable. The transient binding of the N-terminal stretch to the \&beta;<sub>3</sub> strand of the adjacent peptide at the tip is likely to contribute to the arrest phase of the stop-and-go mechanism.</p>},
  year = {2018},
  journal = {The Journal of Physical Chemistry B},
  volume = {122},
  pages = {11072{\textendash}11082},
  month = {2018 Jul 17},
  issn = {1520-5207},
  doi = {10.1021/acs.jpcb.8b05236},
  language = {eng},
}