Tertiary motifs as building blocks for the design of protein-binding peptides.

ABSTRACT: Despite advances in protein engineering, the de novo design of small proteins or peptides that bind to a desired target remains a difficult task. Most computational methods search for binder structures in a library of candidate scaffolds, which can lead to designs with poor target complementarity and low success rates. Instead of choosing from pre-defined scaffolds, we propose that custom peptide structures can be constructed to complement a target surface. Our method mines tertiary motifs (TERMs) from known structures to identify surface-complementing fragments or "seeds." We combine seeds that satisfy geometric overlap criteria to generate peptide backbones and score the backbones to identify the most likely binding structures. We found that TERM-based seeds can describe known binding st

SUBMITTER: Swanson S 

PROVIDER: S-EPMC9088223 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature