An Unfolding Story: AlphaFold's View on Protein Flexibility

ABSTRACT The AlphaFold confidence measures are related to conformation distribution of the protein. Proteome‐wide analyses of predicted local distance difference test (pLDDT) and predicted aligned error (PAE) reveal that proteomes are predominantly ordered on residue level and predominantly disordered on the level of conformation. The fraction of residues in intrinsically disordered regions (IDRs) and the fuzziness of intrinsically folded regions (IFRs) increased upon the evolutionary transition from prokaryotes to eukaryotes, while residual structure in IDRs decreased. All proteins of an organism can be arranged along these three disorder dimensions in a proteome order‐disorder (POD) plot. POD plots reveal that proteomes populate the whole order‐disorder continuum. Fuzziness of IFRs tends to increase with their number in a protein and a distinct subset of intrinsically disordered proteins (IDPs) is a general feature of proteomes.