Bio & PharmaDFTGeometry OptimizationMaterials & EngineeringMolecular DynamicsProteins & PeptidesTransition Metals

Sequence-controlled self-assembly of molecular nanostructures of oligopeptides

Self-assembly of biomolecular nanostructures has inspired the invention and discovery of a rich variety of materials with exceptional properties such as semiconductivity, luminescence or high mechanical rigidity. In particular, peptides and proteins are attractive building blocks for biomolecular self-assembly, because they inherently provide chemical versatility, conformational adaptability and biodegrability.

The conformation as well as the specific interaction of a peptide are defined by its amino-acid sequence. As there exist 20 canonical amino acids, a huge variety of combinations exist, offering a rich playground for bio-engineering. Unfortunately, this rich variety, on the other hand, impedes straight-forward prediction of self-assembled structures by amino-acid sequence alone. There is a need for useful and reliable rules for the rational design of oligopeptides that link amino-acid sequence to the resulting properties.

In a decisive step towards this direction, researchers from the Max Planck Institute for Solid State Research in Stuttgart and the Ecole Polytechnique Federale in Lausanne propose an approach for obtaining microscopic understanding of the self-assembly of an oligopeptide. This approach combines highly resolved scanning tunneling microscopy (STM) measurements with molecular dynamics (MD) and density functional theory (DFT) modelling. This combination of high-resolution microscopy with molecular modelling allows the role of each amino acid in the individual peptide to be addressed.

The researchers demonstrate a deposition scheme, by which oligopeptides form long-range ordered nanostructures in two dimensions on a surface - despite the apparent complexity and flexibility of the underlying molecular building block. On the basis of the submolecular STM resolution that is used to validate the atomistic MD simulations, the researchers obtain detailed models that reveal basic design principles and binding motifs. The researchers emphasize that only by this compound approach they are able to provide a rigorous identification and rationalization of the complex binding motifs. On the basis of this insight, they suggest a reaction mechanism and reveal the effect of sequence manipulation on the self-assembly. This capability is demonstrated by manipulating the sequence of the molecular building block such that long-range ordered hexagonal networks form on the surface.

The researchers conclude that with their approach, the complex self-assembly of oligo- or even small polypeptides at a level that allows rational sequence-controlled fabrication of molecular nanostructures can be understood.