Design of Peptides that Fold and Self-Assemble on Graphite
The graphite-water interface supplies a unique atmosphere for polypeptides that generally favors purchased structures greater than in solution. Therefore, systems composed of designed peptides and graphitic carbon might function as a convenient medium for controlled self-set up of functional materials. Here, we computationally designed cyclic peptides that spontaneously fold right into a ß-sheet-like conformation in the graphite-water interface and self-assemble, so we subsequently observed proof of such set up by atomic pressure microscopy. Utilizing a novel protocol, we screened nearly 2000 sequences, optimizing for formation of the unique folded conformation while discouraging unfolded or misfolded conformations. A mind-to-tail cyclic peptide using the sequence GTGSGTGGPGGGCGTGTGSGPG demonstrated the finest apparent tendency to fold spontaneously, which enhanced sequence was selected for bigger scale molecular dynamics simulations, rigorous free-energy calculations, and experimental validation.
In simulations varying from countless nanoseconds to some couple of microseconds, we observed spontaneous folding of the peptide in the graphite-water interface under a variety of conditions, including multiple temperatures (295 and 370 K), with various initial orientations in accordance with the graphite surface, and taking advantage of different molecular dynamics pressure fields (CHARMM and Amber). The thermodynamic stability from the folded conformation on graphite over a variety of temperatures was verified by replica-exchange simulations and free-energy calculations. However, in free solution, the folded conformation was discovered to be unstable, unfolding in many picoseconds. Intermolecular hydrogen bonds promoted self-set up from the folded peptides into straight line plans in which the peptide backbone exhibited a inclination to align along among the six zigzag directions from the graphite basal plane. For that enhanced peptide, atomic pressure microscopy revealed development of single-molecule-thick straight line patterns of 6-fold symmetry, in conjuction with the simulations, while no such patterns were observed for any control peptide with similar amino acidity Peptide 17 composition however a scrambled sequence.