De novo design of peptides that coassemble into β sheet-based nanofibrils

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 beta-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 similar to 10(6) 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 beta-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.

Automated summary

A computational and experimental approach is used to design pairs of charge-complementary peptides for controllable fabrication of multicomponent biomaterials. Selective coassembly of these pairs into beta-sheet nanofibers or nonfibrillar aggregates is demonstrated through biophysical experiments, showcasing the potential for functional biomaterial design. Solid-state NMR analysis suggests that the designed peptides exhibit a higher degree of structural order compared to previously reported peptides.