Summary
Conformationally stabilizing mutations can be mined from sequence clusters that, when used as a multiple sequence alignment for structure prediction using AlphaFold2, yield the target conformation (1). Authors found three mutations this way that were enriched in clusters, introduced them into the WT of interest, and confirmed by NMR that the protein adopted the target fold.
1.
Wayment-Steele HK, Ojoawo A, Otten R, Apitz JM, Pitsawong W, Hömberger M, et al. Predicting multiple conformations via sequence clustering and AlphaFold2. Nature. 2023;625(7996):832–9. Available from: https://doi.org/10.1038/s41586-023-06832-9