Atomic Scale Structure of Self‐Assembled Lipidated Peptide Nanomaterials

Abstract

Abstractβ‐Peptides have great potential as novel biomaterials and therapeutic agents, due to their unique ability to self‐assemble into low dimensional nanostructures, and their resistance to enzymatic degradation in vivo. However, the self‐assembly mechanisms of β‐peptides, which possess increased flexibility due to the extra backbone methylene groups present within the constituent β‐amino acids, are not well understood due to inherent difficulties of observing their bottom‐up growth pathway experimentally. A computational approach is presented for the bottom‐up modelling of the self‐assembled lipidated β3‐peptides, from monomers, to oligomers, to supramolecular low‐dimensional nanostructures, in all‐atom detail. The approach is applied to elucidate the self‐assembly mechanisms of recently discovered, distinct structural morphologies of low dimensional nanomaterials, assembled from lipidated β3‐peptide monomers. The resultant structures of the nanobelts and the twisted fibrils are stable throughout subsequent unrestrained all‐atom molecular dynamics simulations, and these assemblies display good agreement with the structural features obtained from X‐ray fiber diffraction and atomic force microscopy data. This is the first reported, fully‐atomistic model of a lipidated β3‐peptide‐based nanomaterial, and the computational approach developed here, in combination with experimental fiber diffraction analysis and atomic force microscopy, will be useful in elucidating the atomic scale structure of self‐assembled peptide‐based and other supramolecular nanomaterials.