Fig. 7. Blind predictions of fold-switching proteins.

a Blind predictions are performed by using ColabFold and ESMFold to each predict a structure of an amino acid sequence. ACE predicts coevolved residue pairs using the two predicted structures as references. The predicted structures are compared. Different structure predictions both consistent with coevolutionary predictions fall into Category 1 (b). Examples include the cell division protein MinE and the EF-hand protein EhCaBP. Similar structure predictions with coevolutionary evidence fall into Category 2 (c). Examples include the bacterial pilin protein PapA and the DNA replicase, RepE. For Figures (b) and (c), contact maps are shown above structures predicted by ColabFold (fold-switching regions light gray) and ESMFold (fold-switching regions black). Predicted contacts are teal. In (c) ColabFold and ESMFold predict the same conformation. Predicted contacts corresponding to the experimentally characterized alternative conformation are light purple. Structurally conserved protein regions/common contacts are medium gray. Although all proteins are presented as monomers for simplicity, MinE forms a dimer and PapA forms large oligomers. Figure 1 provides an explanation of the dual-fold contact maps used here. Source data are provided as a Source Data file.