Fig. 5. Screening for fold switching in many protein families predicts a putative alternative fold for the M. tuberculosis secreted protein Mpt53.

a, Overview of the strategy for detecting novel predicted alternative folds. Screening of 628 families with more than 1,000 sequences in their MSA and residue length 48–150 from ref. ³⁰. After clustering, we ran AF2 predictions using ten randomly selected clusters from each. b, Candidates for further sampling were selected by looking for outlier predictions with a high r.m.s.d. to the reference structure and high plDDT. c, Sampled models for candidate Mpt53, visualized using PCA of the closest heavy-atom contacts. Two states with a higher plDDT than the background were observed. d, The top five models by plDDT for the known state (top) and the putative alternative state (bottom), coloured by plDDT per residue. e, The crystal structure of the reduced state of M. tuberculosis Mpt53 (PDB: 1LU4), which corresponds to state 1 in the sampled landscape (top). In the putative alternative state 2, strand β1 replaces β5 in the five-strand β-sheet. Helix α4 shifts to the other side of the β-sheet and helix α5 is displaced.