Critical assessment of protein intrinsic disorder prediction

Nat Methods. 2021 May;18(5):472-481. doi: 10.1038/s41592-021-01117-3. Epub 2021 Apr 19.

Abstract

Intrinsically disordered proteins, defying the traditional protein structure-function paradigm, are a challenge to study experimentally. Because a large part of our knowledge rests on computational predictions, it is crucial that their accuracy is high. The Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment was established as a community-based blind test to determine the state of the art in prediction of intrinsically disordered regions and the subset of residues involved in binding. A total of 43 methods were evaluated on a dataset of 646 proteins from DisProt. The best methods use deep learning techniques and notably outperform physicochemical methods. The top disorder predictor has Fmax = 0.483 on the full dataset and Fmax = 0.792 following filtering out of bona fide structured regions. Disordered binding regions remain hard to predict, with Fmax = 0.231. Interestingly, computing times among methods can vary by up to four orders of magnitude.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Computational Biology*
  • Databases, Protein
  • Intrinsically Disordered Proteins / chemistry*
  • Protein Binding
  • Protein Conformation
  • Protein Folding
  • Software

Substances

  • Intrinsically Disordered Proteins