Sequence-Dependent Nanofiber Structures of Phenylalanine and Isoleucine Tripeptides.
The molecular design of short peptides to achieve a tailor-made functional architecture has attracted attention during the past decade but remains challenging as a result of insufficient understanding of the relationship between peptide sequence and assembled supramolecular structures. We report a hybrid-resolution model to computationally explore the sequence-structure relationship of self-assembly for tripeptides containing only phenylalanine and isoleucine. We found that all these tripeptides have a tendency to assemble into nanofibers composed of laterally associated filaments. Molecular arrangements within the assemblies are diverse and vary depending on the sequences. This structural diversity originates from (1) distinct conformations of peptide building blocks that lead to different surface geometries of the filaments and (2) unique sidechain arrangements at the filament interfaces for each sequence. Many conformations are available for tripeptides in solution, but only an extended β-strand and another resembling a right-handed turn are observed in assemblies. It was found that the sequence dependence of these conformations and the packing of resulting filaments are determined by multiple competing noncovalent forces, with hydrophobic interactions involving Phe being particularly important. The sequence pattern for each type of assembly conformation and packing has been identified. These results highlight the importance of the interplay between conformation, molecular packing, and sequences for determining detailed nanostructures of peptides and provide a detailed insight to support a more precise design of peptide-based nanomaterials.
['Xiong|Qinsi|Q|', 'Liu|Ziye|Z|', 'Han|Wei|W|0000-0003-0759-1766']
D000595:Amino Acid Sequence D015195:Drug Design D057927:Hydrophobic and Hydrophilic Interactions D007532:Isoleucine D008855:Microscopy, Electron, Scanning D056004:Molecular Dynamics Simulation D057139:Nanofibers D036103:Nanotechnology D009842:Oligopeptides D010649:Phenylalanine D011487:Protein Conformation D015202:Protein Engineering D055503:Protein Multimerization
conformational dependence hybrid-resolution force field molecular dynamics simulation peptide self-assembly sequence–structure relationship