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

• Published in: Science advances Vol. 7; no. 36; p. eabf7668
• Main Authors: Xiao, Xingqing, Wang, Yiming, Seroski, Dillon T, Wong, Kong M, Liu, Renjie, Paravastu, Anant K, Hudalla, Gregory A, Hall, Carol K
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 03.09.2021
• Subjects: Biochemistry; Biomedicine and Life Sciences; Materials Science; SciAdv r-articles
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.abf7668

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 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.