Supramolecular structure of helical ribbons self-assembled from a β-sheet peptide

Abstract

We have investigated the supramolecular structure of helical ribbons formed during self-assembly of a ␤-sheet peptide using computer simulation. We tested a wide range of molecular packing geometries consistent with the experimental dimensions to identify the most stable structure, and then systematically changed the helical geometry to investigate its energy landscape. The effect of pH was incorporated by scaling the amount of charge on the side chains based on the electrostatic double layer theory. Our results suggest that these left-handed helical ribbons are comprised of a double ␤-sheet and that the experimentally measured dimensions correspond to a local energy minimum. Side chain interactions are found to be critical in determining the stability and curvature of the helix. Our approach has general applicability to the study of self-assembled nanostructures from ␤-sheet peptides where high resolution data are not yet available.

Kinetic control of dimer structure formation in amyloid fibrillogenesis

“…Its dipole moment is significantly lower than the actual peptides (6.4 Debyes versus 52-100 Debyes measured from the center of geometry) and the simulation showed reduced preference for the antiparallel configuration; it was found to be 52.5%, compared to 60.2% for A␤ 7g . Although the preference for an antiparallel configuration is slight at the dimer level, the distinction in fibrils is likely to be cooperative in nature so that the bias could become stronger for more extended ␤-sheet structures (20,27). For example, in previous simulations of a ␤-sheet formed from 40 KFE8 monomers, it was found that an antiparallel ␤-sheet maintained its structure, whereas a parallel ␤-sheet did not (27).…”

“…Although the preference for an antiparallel configuration is slight at the dimer level, the distinction in fibrils is likely to be cooperative in nature so that the bias could become stronger for more extended ␤-sheet structures (20,27). For example, in previous simulations of a ␤-sheet formed from 40 KFE8 monomers, it was found that an antiparallel ␤-sheet maintained its structure, whereas a parallel ␤-sheet did not (27).…”

“…The other peptides are designed sequences used in the study of fibril formation and peptide self-assembly. A␤ 7 , K I , and KFE8 form antiparallel ␤-sheet structures (26)(27)(28), whereas K L forms ␤-sheet aggregates but not fibrils (26). Several peptides were studied to determine sequence-independent characteristics of the dimerization process, because, as already mentioned, many different proteins and peptides can form amyloid fibrils (23,29).…”

Investigating the Effects of Aromatic Amino Acids on Amphipathic Peptide Self-Assembly and Emergent Hydrogel Viscoelasticity

“…Amphipathic β-sheet peptides composed of alternating hydrophobic and hydrophilic amino acids (with general sequence (XZXZ)n where X is nonpolar and Z is polar) are a privileged class of self-assembling peptide that have been widely used in the design of hydrogel materials [4]. The (FKFE)2 peptide is a prominent member of this class of material that has been frequently studied [5,6]. This peptide self-assembles into putative β-sheet bilayer nanoribbons; molecular dynamics studies suggest that the alignment of peptides within the β-sheet structure requires the N-terminal Phe residue to "dangle" out of register ( Figure 1) [6].…”

“…The (FKFE)2 peptide is a prominent member of this class of material that has been frequently studied [5,6]. This peptide self-assembles into putative β-sheet bilayer nanoribbons; molecular dynamics studies suggest that the alignment of peptides within the β-sheet structure requires the N-terminal Phe residue to "dangle" out of register ( Figure 1) [6]. We have adopted this peptide specifically to understand the impact of general hydrophobic and more specific aromatic π-π effects on peptide self-assembly [7,8].…”