Computational Design of Single-Peptide Nanocages with Nanoparticle Templating
Date
2022-02-12
Journal Title
Journal ISSN
Volume Title
Publisher
Molecules
Abstract
Protein complexes perform a diversity of functions in natural biological systems. While computational protein design has enabled the development of symmetric protein complexes with spherical shapes and hollow interiors, the individual subunits often comprise large proteins. Peptides have also been applied to self-assembly, and it is of interest to explore such short sequences as building blocks of large, designed complexes. Coiled-coil peptides are promising subunits as they have a symmetric structure that can undergo further assembly. Here, an α-helical 29-residue peptide that forms a tetrameric coiled coil was computationally designed to assemble into a spherical cage that is approximately 9 nm in diameter and presents an interior cavity. The assembly comprises 48 copies of the designed peptide sequence. The design strategy allowed breaking the side chain conformational symmetry within the peptide dimer that formed the building block (asymmetric unit) of the cage. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) techniques showed that one of the seven designed peptide candidates assembled into individual nanocages of the size and shape. The stability of assembled nanocages was found to be sensitive to the assembly pathway and final solution conditions (pH and ionic strength). The nanocages templated the growth of size-specific Au nanoparticles. The computational design serves to illustrate the possibility of designing target assemblies with pre-determined specific dimensions using short, modular coiled-coil forming peptide sequences.
Description
This article was originally published in Molecules. The version of record is available at: https://doi.org/10.3390/molecules27041237
Keywords
peptides, self-assembly, molecular cages, computational design, biomaterials
Citation
Villegas, José A., Nairiti J. Sinha, Naozumi Teramoto, Christopher D. Von Bargen, Darrin J. Pochan, and Jeffery G. Saven. 2022. "Computational Design of Single-Peptide Nanocages with Nanoparticle Templating" Molecules 27, no. 4: 1237. https://doi.org/10.3390/molecules27041237