430048 Oligomer Formation of Toxic and Functional Amyloid Peptides Studied with Atomistic Simulations (Rapid Fire)

Wednesday, November 11, 2015
Exhibit Hall 1 (Salt Palace Convention Center)
Martin Carballo Pacheco, RWTH Aachen University, Aachen, Germany, Ahmed E. Ismail, Aachener Verfahrenstechnik, Faculty of Mechanical Engineering, RWTH Aachen University, Aachen, Germany and Birgit Strodel, Forschungzentrum Jülich, Jülich, Germany

While amyloids have traditionally been associated with diseases such as Alzheimer's, it has recently been discovered that they play functional roles as well, including  storage of peptide hormones. The differences between aberrant and functional amyloids remain unclear, but soluble oligomers formed during amyloid aggregation are known to be more toxic than the final fibrils. We have performed molecular dynamics simulations to study the aggregation of three different peptides: the amyloid-β peptide Aβ25-35, which is associated with Alzheimer's disease, and two functional amyloid-forming tachykinin peptides, kassinin and neuromedin K. Although the three peptides have very similar primary sequences, the tachykinin peptides, unlike Aβ25-35, form non-toxic amyloids. Our simulations suggest that the C-terminus charge is essential in controlling the aggregation process. In particular, if the kassinin C-terminus is not amidated, the kinetics slow down considerably. In addition, we observe that, in extended conformations, the monomeric peptides aggregate faster than the corresponding peptides in collapsed hairpin-like conformations.

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See more of this Session: Poster Session: Bioengineering
See more of this Group/Topical: Food, Pharmaceutical & Bioengineering Division