De novo design of peptides that coassemble into β sheet-based nanofibrils.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34516924.
- Also identified by DOI 10.1126/sciadv.abf7668 and PMC identifier 8442925.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Peptides’ hierarchical coassembly into nanostructures enables controllable fabrication of multicomponent biomaterials. In this work, we describe a computational and experimental approach to design pairs of charge-complementary peptides that selectively coassemble into β-sheet nanofibers when mixed together but remain unassembled when isolated separately. The key advance is a peptide coassembly design (PepCAD) algorithm that searches for pairs of coassembling peptides. Six peptide pairs are identified from a pool of ~10<sup>6</sup> candidates via the PepCAD algorithm and then subjected to DMD/PRIME20 simulations to examine their co-/self-association kinetics. The five pairs that spontaneously aggregate in kinetic simulations selectively coassemble in biophysical experiments, with four forming β-sheet nanofibers and one forming a stable nonfibrillar aggregate. Solid-state NMR, which is applied to characterize the coassembling pairs, suggests that the in silico peptides exhibit a higher degree of structural order than the previously reported CATCH(+/−) peptides.