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Can AlphaFold2 predict the impact of missense mutations on structure?

Nature Structural & Molecular Biology volume 29, pages 1–2 (2022)Cite this article

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To the Editor — Understanding the impact that missense mutations have on protein structure helps to reveal their biological effects. Although the structural prediction algorithm of AlphaFold2 is able to predict wild-type (WT) structures to high accuracy, it seems to fall short in predicting the impact of missense mutations on the three-dimensional (3D) structures of proteins.

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Fig. 1: Interpretation of structure-disrupting mutations by AlphaFold2.

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Acknowledgements

We are grateful to H. Matsuo for critical reading of the manuscript. This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH) (1ZIABC011627 to K.J.W.), and used computational resources of the High-Performance Computing Biowulf cluster of the NIH (http://hpc.nih.gov).

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  1. Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA

    Gwen R. Buel & Kylie J. Walters

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  1. Gwen R. Buel
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  2. Kylie J. Walters
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Correspondence to Kylie J. Walters.

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Buel, G.R., Walters, K.J. Can AlphaFold2 predict the impact of missense mutations on structure?. Nat Struct Mol Biol 29, 1–2 (2022). https://doi.org/10.1038/s41594-021-00714-2

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