Systematic identification of conditionally folded intrinsically disordered regions by AlphaFold2

The AlphaFold Protein Structure Database contains predicted structures for millions of proteins. For the majority of human proteins that contain intrinsically disordered regions (IDRs), which do not adopt a stable structure, it is generally assumed that these regions have low AlphaFold2 confidence scores that reflect low-confidence structural predictions. Here, we show that AlphaFold2 assigns confident structures to nearly 15% of human IDRs. By comparison to experimental NMR data for a subset of IDRs that are known to conditionally fold (i.e., upon binding or under other specific conditions), we find that AlphaFold2 often predicts the structure of the conditionally folded state. Based on databases of IDRs that…

• UO
  University of Wisconsin-Madison
• CF
  Canada Foundation for Innovation
• HF
  Hospital for Sick Children
• KG
  Karl-Franzens-Universität Graz
• MU
  Medizinische Universität Graz
• NI
  National Institutes of Health

  Award: P41GM111135
• CI
  Canadian Institutes of Health Research

  Awards: 148375, FDN-148375, -148375, PJT-148532
• NI
  National Institute of General Medical Sciences

  Award: P41GM111135