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arXiv · 2204.06860

AlphaFold2 can predict single-mutation effects

John M. McBride·Konstantin Polev·Amirbek Abdirasulov·Vladimir Reinharz·Bartosz A. Grzybowski·Tsvi Tlusty
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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 \num{3901} experimental and AF-predicted structures. Furthermore, analysis of ${\sim} 11000$ 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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John M. McBride, Konstantin Polev, Amirbek Abdirasulov, Vladimir Reinharz, Bartosz A. Grzybowski, Tsvi Tlusty. 2023-10-21. AlphaFold2 can predict single-mutation effects. https://arxiv.org/abs/2204.06860

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