The self-assembly of surfactant-like peptides containing 4−10 glycines as the component of the hydrophobic tails and aspartic acids as the hydrophilic heads is described. The peptide monomers form nanotubes and nanovesicles in water at neutral pH. These nanostructures become more polydisperse as the length of the glycine tails increases. These unique structures may serve not only as scaffolds for constructing diverse nanodevices but also as enclosures to encapsulate rudimentary enzymes for studying prebiotic molecular evolution.
We report the observation of intermediate structures in the self-assembly of the peptide KFE8 (FKFEFKFE), designed with alternating polar and nonpolar amino acids. Self-assembly was followed over time using atomic force microscopy (AFM), transmission electron microscopy (TEM), and circular dichroism (CD). Molecular dynamics simulations suggest that these intermediates are left-handed double helical β-sheets. These findings have implications in the study of β-sheet fibril formation, and in the molecular design of materials.
Amyloid fibril formation involves nonfibrillar oligomeric intermediates, which are important as possible cytotoxic species in neurodegenerative diseases. However, their transient nature and polydispersity have made it difficult to identify their formation mechanism or structure. We have investigated the dimerization process, the first step in aggregate formation, by multiple molecular dynamics simulations of five -sheet-forming peptides. Contrary to the regular -sheet structure of the amyloid fibril, the dimers exhibit all possible combinations of -sheets, with an overall preference for antiparallel arrangements. Through statistical analysis of 1,000 dimerization trajectories, each 1 ns in length, we have demonstrated that the observed distribution of dimer configurations is kinetically determined; hydrophobic interactions orient the peptides so as to minimize the solvent accessible surface area, and the dimer structures become trapped in energetically unfavorable conformations. Once the hydrophobic contacts are present, the backbone hydrogen bonds form rapidly by a zipper-like mechanism. The initial nonequilibrium structures formed are stable during the 1-ns simulation time for all five peptides at room temperature. In contrast, at higher temperatures, where rapid equilibration among different configurations occurs, the distribution follows the global energies. The relaxation time of dimers at room temperature was estimated to be longer than the time for diffusional encounters with other oligomers at typical concentrations. These results suggest that kinetic trapping could play a role in the structural evolution of early aggregates in amyloid fibrillogenesis.
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