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AlphaFold2: A role for disordered protein prediction?

View ORCID ProfileCarter J. Wilson, View ORCID ProfileWing-Yiu Choy, View ORCID ProfileMikko Karttunen
doi: https://doi.org/10.1101/2021.09.27.461910
Carter J. Wilson
†Department of Mathematics, The University of Western Ontario, 1151 Richmond Street, Canada, N6A 5B7
‡Centre for Advanced Materials and Biomaterials Research, The University of Western Ontario, 1151 Richmond Street, London, Ontario, Canada, N6A 5B7
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Wing-Yiu Choy
¶Department of Biochemistry, The University of Western Ontario, 1151 Richmond Street, Canada, N6A 5C1
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Mikko Karttunen
§Department of Chemistry, The University of Western Ontario, 1151 Richmond Street, Canada, N6A 3K7
‖Department of Physics and Astronomy, The University of Western Ontario, 1151 Richmond Street, Canada, N6A 5B7
‡Centre for Advanced Materials and Biomaterials Research, The University of Western Ontario, 1151 Richmond Street, London, Ontario, Canada, N6A 5B7
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  • For correspondence: mkarttu@uwo.ca
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Abstract

The development of AlphaFold2 was a paradigm-shift in the structural biology community; herein we assess the ability of AlphaFold2 to predict disordered regions against traditional sequence-based disorder predictors. We find that a näaive use of Dictionary of Secondary Structure of Proteins (DSSP) to separate ordered from disordered regions leads to a dramatic overestimation in disorder content, and that the predicted Local Distance Difference Test (pLDDT) provides a much more rigorous metric. In addition, we show that even when used for disorder prediction, conventional predictors can outperform the pLDDT in disorder identification, and note an interesting relationship between the pLDDT and secondary structure, that may explain our observations, and hints at a broader application of the pLDDT to IDP dynamics.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* E-mail: jchoy4{at}uwo.ca; mkarttu{at}uwo.ca

  • There was a typo that propagated through the manuscript regarding Predicted Aligned Error (PAE) and predicted Local Distance Difference Test (pLDDT). The latter term is what should have been used in the manuscript and that has been corrected in this revised version.

  • https://github.com/SoftSimu/AlphaFoldDisorderData

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 17, 2021.
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AlphaFold2: A role for disordered protein prediction?
Carter J. Wilson, Wing-Yiu Choy, Mikko Karttunen
bioRxiv 2021.09.27.461910; doi: https://doi.org/10.1101/2021.09.27.461910
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AlphaFold2: A role for disordered protein prediction?
Carter J. Wilson, Wing-Yiu Choy, Mikko Karttunen
bioRxiv 2021.09.27.461910; doi: https://doi.org/10.1101/2021.09.27.461910

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