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bioRxiv · 10.1101/2022.04.14.488301

AlphaFold2 can predict structural and phenotypic effects of single mutations

Mcbride, J. M.·Reinharz, V.·Polev, K.·Grzybowski, B. A.·Tlusty, T.
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Abstract

AlphaFold2 (AF) is a promising tool, but is it accurate enough to predict single mutation effects? Here, we report that the localized structural deformation between protein pairs differing by only 1-3 mutations - as measured by the effective strain - is correlated across 3,901 experimental and AF-predicted structures. Furthermore, analysis of [~]11,000 proteins shows that the local structural change correlates with various phenotypic changes. These findings suggest that AF can predict the range and magnitude of single-mutation effects on average, and we propose a method to improve precision of AF predictions and to indicate when predictions are unreliable.

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Mcbride, J. M., Reinharz, V., Polev, K., Grzybowski, B. A., Tlusty, T.. 2022-04-14. AlphaFold2 can predict structural and phenotypic effects of single mutations. https://doi.org/10.1101/2022.04.14.488301

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