De novo design of knotted tandem repeat proteins.

ABSTRACT: De novo protein design methods can create proteins with folds not yet seen in nature. These methods largely focus on optimizing the compatibility between the designed sequence and the intended conformation, without explicit consideration of protein folding pathways. Deeply knotted proteins, whose topologies may introduce substantial barriers to folding, thus represent an interesting test case for protein design. Here we report our attempts to design proteins with trefoil (3₁) and pentafoil (5₁) knotted topologies. We extended previously described algorithms for tandem repeat protein design in order to construct deeply knotted backbones and matching designed repeat sequences (N = 3 repeats for the trefoil and N = 5 for the pentafoil). We confirmed the intended conforma

SUBMITTER: Doyle LA 

PROVIDER: S-EPMC10598012 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature