AlphaFold2 can predict single-mutation effects
John M. McBride, Konstantin Polev, Amirbek Abdirasulov, Vladimir Reinharz, Bartosz A. Grzybowski, Tsvi Tlusty
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- github.com/mirabdi/pdanalysisOfficialIn papernone★ 33
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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 3901 experimental and AF-predicted structures. Furthermore, analysis of 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.