@article{bibcite_169,
  keywords = {Kinetics, Peptides, Thermodynamics, Amyloid, Protein Structure, Quaternary, Amyloid beta-Peptides},
  author = {R. Pellarin and A. Caflisch},
  title = {Interpreting the aggregation kinetics of amyloid peptides},
  abstract = {<p>Amyloid fibrils are insoluble mainly \&beta;-sheet aggregates of proteins or peptides. The multi-step process of amyloid aggregation is one of the major research topics in structural biology and biophysics because of its relevance in protein misfolding diseases like Alzheimer{\textquoteright}s, Parkinson{\textquoteright}s, Creutzfeld-Jacob{\textquoteright}s, and type II diabetes. Yet, the detailed mechanism of oligomer formation and the influence of protein stability on the aggregation kinetics are still matters of debate. Here a coarse-grained model of an amphipathic polypeptide, characterized by a free energy profile with distinct amyloid-competent (<i>i.e.</i> \&beta;-prone) and amyloid-protected states, is used to investigate the kinetics of aggregation and the pathways of fibril formation. The simulation results suggest that by simply increasing the relative stability of the \&beta;-prone state of the polypeptide, disordered aggregation changes into fibrillogenesis with the presence of oligomeric on-pathway intermediates, and finally without intermediates in the case of a very stable \&beta;-prone state. The minimal-size aggregate able to form a fibril is generated by collisions of oligomers or monomers for polypeptides with unstable or stable \&beta;-prone state, respectively. The simulation results provide a basis for understanding the wide range of amyloid-aggregation mechanisms observed in peptides and proteins. Moreover, they allow us to interpret at a molecular level the much faster kinetics of assembly of a recently discovered functional amyloid with respect to the very slow pathological aggregation.</p>},
  year = {2006},
  journal = {Journal of Molecular Biology},
  volume = {360},
  pages = {882-892},
  month = {2006 Jul 21},
  issn = {0022-2836},
  doi = {10.1016/j.jmb.2006.05.033},
  language = {eng},
}