title: Oligomer Formation of Toxic and Functional Amyloid Peptides Studied with Atomistic Simulations.
abstract: Amyloids are associated with diseases, including Alzheimer's, as well as functional roles such as storage of peptide hormones. It is still unclear what differences exist between aberrant and functional amyloids. However, it is known that soluble oligomers formed during amyloid aggregation are more toxic than the final fibrils. Here, we perform molecular dynamics simulations to study the aggregation of the amyloid-β peptide Aβ25-35, associated with Alzheimer's disease, and two functional amyloid-forming tachykinin peptides: kassinin and neuromedin K. Although the three peptides have similar primary sequences, tachykinin peptides, in contrast to Aβ25-35, form nontoxic amyloids. Our simulations reveal that the charge of the C-terminus is essential to controlling the aggregation process. In particular, when the kassinin C-terminus is not amidated, the aggregation kinetics decreases considerably. In addition, we observe that the monomeric peptides in extended conformations aggregate faster than those in collapsed hairpin-like conformations.
authors.affiliation: †AICES Graduate School and Aachener Verfahrenstechnik: Molecular Simulations and Transformations, RWTH Aachen University, Schinkelstraße 2, 52062 Aachen, Germany.|‡Institute of Complex Systems: Structural Biochemistry (ICS-6), Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.
authors.forename: Martín
authors.initials: M
authors.lastname: Carballo-Pacheco
authors.affiliation: †AICES Graduate School and Aachener Verfahrenstechnik: Molecular Simulations and Transformations, RWTH Aachen University, Schinkelstraße 2, 52062 Aachen, Germany.
authors.forename: Ahmed E
authors.initials: AE
authors.lastname: Ismail
authors.affiliation: ‡Institute of Complex Systems: Structural Biochemistry (ICS-6), Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.|¶Institute of Theoretical and Computational Chemistry, Heinrich Heine University Düsseldorf, Universitätstraße 1, 40225 Düsseldorf, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Strodel
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D015286:Kassinin / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D015287:Neurokinin B / Q000737:chemistry*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D015286:Kassinin; D015287:Neurokinin B