title: Atomic-scale simulations confirm that soluble beta-sheet-rich peptide self-assemblies provide amyloid mimics presenting similar conformational properties.
abstract: The peptide self-assembly mimic (PSAM) from the outer surface protein A (OspA) can form highly stable but soluble beta-rich self-assembly-like structures similar to those formed by native amyloid-forming peptides. However, unlike amyloids that predominantly form insoluble aggregates, PSAMs are highly water-soluble. Here, we characterize the conformations of these soluble beta-sheet-rich assemblies. We simulate PSAMs with different-sized beta-sheets in the presence and absence of end-capping proteins using all-atom explicit-solvent molecular dynamics, comparing the structural stability, conformational dynamics, and association force. Structural and free-energy comparisons among beta-sheets with different numbers of layers and sequences indicate that in similarity to amyloids, the intersheet side chain-side chain interactions and hydrogen bonds combined with intrasheet salt bridges are the major driving forces in stabilizing the overall structural organization. A detailed structural analysis shows that in similarity to amyloid fibrils, all wild-type and mutated PSAM structures display twisted and bent beta-sheets to some extent, implying that a twisted and bent beta-sheet is a general motif of beta-rich assemblies. Thus, our studies indicate that soluble beta-sheet-rich peptide self-assemblies can provide good amyloid mimics, and as such confirm on the atomic scale that they are excellent systems for amyloid studies. These results provide further insight into the usefulness of such mimics for nanostructure design.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Akron, Akron, Ohio, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Yu
authors.forename: Jingdai
authors.initials: J
authors.lastname: Wang
authors.forename: Jui-Chen
authors.initials: JC
authors.lastname: Yang
authors.forename: Qiuming
authors.initials: Q
authors.lastname: Wang
authors.forename: Stephen Z D
authors.initials: SZ
authors.lastname: Cheng
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure*; D000954:Antigens, Surface / Q000737:chemistry* / Q000648:ultrastructure*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D001428:Bacterial Vaccines / Q000737:chemistry*; D001665:Binding Sites; D003198:Computer Simulation; D019281:Dimerization; D008074:Lipoproteins / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000648:ultrastructure; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D016229:Amyloid beta-Peptides; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008074:Lipoproteins; D046912:Multiprotein Complexes; C072045:OspA protein