PT - JOURNAL ARTICLE AU - Carter J. Wilson AU - Wing-Yiu Choy AU - Mikko Karttunen TI - AlphaFold2: A role for disordered protein prediction? AID - 10.1101/2021.09.27.461910 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.09.27.461910 4099 - http://biorxiv.org/content/early/2021/10/17/2021.09.27.461910.short 4100 - http://biorxiv.org/content/early/2021/10/17/2021.09.27.461910.full AB - 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 StatementThe authors have declared no competing interest.