(667h) Molecular Insights Into Diphenylalanine Nanotube Assembly: All-Atom Simulations of Oligomerization

The simple diphenylalanine (FF) peptide self-assembles in aqueous solutions into nanotubes (FFNTs) with remarkable strength, thermal stability and other promising physical properties. FFNTs have found use in many applications, including as sacrificial templates and scaffolds for structuring inorganic materials, and as new hydrogels and biosensors. FFNTs can also form on substrates using vapor-deposition in vacuum, to create dense FF-nanoforests that have already found use in super-hydrophobic surfaces and high-performance supercapacitors. However, little is known about assembly mechanisms of FFNTs or the forces underlying their stability.

    Here, we use detailed molecular simulations to study the early self-assembly stages of FF in water and in vacuum. First, we perform a variety of molecular dynamics (MD) simulations on small-oligomer formation in water and assess the balance of hydrogen bonds, electrostatic interactions, and side chain aromatic or hydrophobic forces, as well as the emergent structural motifs. We find that while electrostatic interactions steer FF peptides into more ordered dimers and trimers, the hydrophobic side chain interactions play a strong role in determining the structures of larger oligomers. However, capped (uncharged) versions of the peptide display dramatically different assembly behavior, and emphasize the importance of amphiphilicity to FF assembly. By comparing these results to simulations of the experimental FFNT X-ray crystal structure, we propose that the early structural templates to be formed are more amphiphili-like, rather than the salt-bridge-stabilized hexamer ring motif that has been proposed in the literature.

    Second, we study the assembly of FF peptides in vacuum. During the vaporization process, the linear backbone of FF peptides is cyclized, and so its chemical structure is distinct from that in solution. We find that cyclo-FF molecules indeed have strong preferences to form vertically aligned ladder-like structures stitched together by hydrogen bonds. Such structures are reminiscent of the solution-phase oligomers, but appear much more stable. Importantly, the obtained ladder structures have some structural similarities with the crystal structure of cyclo-FF nanowires, although future work mush address how these ladders pack in a way to form nanotubes. In total, our results suggest novel pathways for assembly of FF in different environments and offer plausible explanations for the interactions that drive their unique properties.