Summary
Nearly half (43.7%) of CATH domains do not pass designability filters used to evaluate whether protein backbone design methods work or not (1). Designability here refers to designing a sequence onto the structure using inverse folding, followed by forward folding using a protein structure prediction model. This finding is true even when using the native sequence with ESMFold; with AlphaFold2 in single-sequence mode, the number drops to 1.34% for native sequences.
1.
Lu T, Liu M, Chen Y, Kim J, Huang P-S. Assessing generative model coverage of protein structures with SHAPES. Cell Systems. 2025;16(8):101347. Available from: https://doi.org/10.1016/j.cels.2025.101347