Summary
Most alpha/beta topologies enumerated by (1) are not explored by nature. These include 12,348 that can be achieved without significant spatial violations, but only 400 combinations are observed in the extant fold space (for example Top7). This is said to correspond to a lower limit.
Details
It is unclear if this is due to the “Survival of the flattest” effect (e.g., these proteins are not evolvable), or if it is because they have trouble folding. These were then generated using Rosetta. AlphaFold2 was unable to fold some of them accurately.
Figures
Ref (1)
1.
Minami S, Kobayashi N, Sugiki T, Nagashima T, Fujiwara T, Tatsumi-Koga R, et al. Exploration of novel αβ-protein folds through de novo design. Nature Structural & Molecular Biology. 2023;30(8):1132–40. Available from: https://doi.org/10.1038/s41594-023-01029-0