De novo design of peptides that coassemble into ß sheet-based nanofibrils.
Sci Adv
; 7(36): eabf7668, 2021 Sep 03.
Article
in En
| MEDLINE
| ID: mdl-34516924
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 ß-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 ~106 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 ß-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Sci Adv
Year:
2021
Document type:
Article
Affiliation country:
Estados Unidos