All-Atom Molecular Dynamics Simulations of Peptide Amphiphile Assemblies That Spontaneously Form Twisted and Helical Ribbon Structures

Abstract

Self-assembly of peptide amphiphiles (PAs) has been an active research area as the assemblies can be programmed into variously shaped nanostructures. Although cylindrical micelles are common structures, gold-binding peptide conjugates can self-assemble into chiral nanofibers with single or double helices. When gold nanoparticles bind to the helices, the resulting chiral nanoparticle assemblies have a collective plasmonic circular dichroism signal that can serve as nanoscale circular polarizers or chiroptical sensors. A better atomic-level understanding of the factors which lead to helical PA assemblies is therefore of significant importance. In this study we show that all-atom molecular dynamics simulations can describe the spontaneous structural transformation from a planar assembly of PAs to a twisted assembly or to a helical ribbon. The twist angle and the helical diameter calculated from the simulations closely match the experimental results, with the oxidation of a single Met residue in each PA leading to a change from bilayer to monolayer assemblies with significantly different ribbon properties. A secondary structure analysis shows how a combination of β-sheet formation near the hydrophobic core of the micelle and PPII structures from proline-rich C-terminus regions favors helix formation. The simulations presented here demonstrate the capability of predicting self-assembly in chiral structures, protocols that can easily be applied to the assembly of other amphiphilic molecules.

Supramolecular Interactions and Morphology of Self-Assembling Peptide Amphiphile Nanostructures

“…42−44 The AFM height trace of wider nanostructures is characteristic of twisted ribbonlike nanostructures, 45 and comparisons with Cryo-TEM images of structures with similar dimensions confirm this morphology (Figure 1d). While previous studies have considered PA nanostructures as cylindrical, 42−44 aggregates of cylinders, 46 or wide ribbonlike stacks of βsheets, 10,12,47 the experimentally observed structures seen here suggest a crossover from cylindrical fibers to ribbons. The ribbons are too narrow to be a stack of multiple cylinders, and there is no indication of stepwise increase in width as observed…”

Molecular simulations of self-assembling bio-inspired supramolecular systems and their connection to experiments

“…A property that shows up in many pre-assembled peptide or PA fibres is spontaneous twisting, 175 – 178 also seen in experimental studies using AFM, TEM and CD spectroscopy. Lai, Rosi and Schatz simulated the formation of chiral nanofibers of a self-assembling gold-binding peptide conjugate, starting from achiral structures using atomistic MD and found the correct handedness and pitch.…”

“…Lai, Rosi and Schatz simulated the formation of chiral nanofibers of a self-assembling gold-binding peptide conjugate, starting from achiral structures using atomistic MD and found the correct handedness and pitch. 175 Frederix et al took a similar approach and identified the handedness and pitch of stacks of peptide macrocycles. 54 A still relatively unexplored area is the interaction between fibres.…”

Guiding principles for peptide nanotechnology through directed discovery

“…92,101 However, these simulations do reveal the importance of dynamic effects in the assembly process and as such have contributed significantly to the understanding of selfassembled systems. Therefore, in order to use information obtained from atomistic MD simulations in directed discovery endeavours there are two basic approaches: (i) to use a smaller model system (e.g., < 100 peptides) to study how the building blocks interact in a locally realistic environment; 35,89,90,[94][95][96][97][98][99][100]133 or (ii) to create model systems with a presumed structure and test the stability. 46,73,74,134,135…”