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Keyword: structural plasticity ×Clear all

3 claims from 1 paper

1. Biochemistry, Genetics and Molecular Biology › Protein Structure and Dynamics

   Systematic identification of conditionally folded intrinsically disordered regions by AlphaFold2

   Alderson, Pritišanac, Kolarić, Moses and Forman-Kay · Proceedings of the National Academy of Sciences · 2023

   The paper examines AlphaFold2's confident predictions for human disordered protein regions and finds they often correspond to conditionally folded states, with links to disease mutations and differences between kingdoms.

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   1. UncheckedCompared with NMR data for IDRs known to fold conditionally, AlphaFold2 often predicts the structure of their conditionally folded state.“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.”
   2. UncheckedUsing known conditionally folding disordered regions as a benchmark, AlphaFold2 is estimated to flag them at up to 88% precision with a 10% false positive rate.“Based on databases of IDRs that are known to conditionally fold, we estimate that AlphaFold2 can identify conditionally folding IDRs at a precision as high as 88% at a 10% false positive rate, which is remarkable considering that conditionally folded IDR structures were minimally represented in its…”
   3. Unchecked“We find that human disease mutations are nearly fivefold enriched in conditionally folded IDRs over IDRs in general and that up to 80% of IDRs in prokaryotes are predicted to conditionally fold, compared to less than 20% of eukaryotic IDRs.”