De novo design of modular peptide-binding proteins by superhelical matching.

ABSTRACT: General approaches for designing sequence-specific peptide-binding proteins would have wide utility in proteomics and synthetic biology. However, designing peptide-binding proteins is challenging, as most peptides do not have defined structures in isolation, and hydrogen bonds must be made to the buried polar groups in the peptide backbone^1-3. Here, inspired by natural and re-engineered protein-peptide systems^4-11, we set out to design proteins made out of repeating units that bind peptides with repeating sequences, with a one-to-one correspondence between the repeat units of the protein and those of the peptide. We use geometric hashing to identify protein backbones and peptide-docking arrangements that are compatible with bidentate hydrogen bonds between the side ch

SUBMITTER: Wu K 

PROVIDER: S-EPMC10115654 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature