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 ∼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.
Cite
@article{arxiv.2204.06860,
title = {AlphaFold2 can predict single-mutation effects},
author = {John M. McBride and Konstantin Polev and Amirbek Abdirasulov and Vladimir Reinharz and Bartosz A. Grzybowski and Tsvi Tlusty},
journal= {arXiv preprint arXiv:2204.06860},
year = {2023}
}