AlphaFold2 can predict single-mutation effects on structure and phenotype

Abstract

AlphaFold2 (AF) is a promising tool, but is it accurate enough to predict single mutation effects? Here, we report that a measure for localized structural deformation between protein pairs differing by only 1-3 mutations is correlated across 4,645 experimental and AF-predicted structures. Furthermore, analysis of ∼10,000 proteins shows that the local structural change correlates with various phenotypic changes. These findings suggest that AF can predict the magnitude of single-mutation effects in many proteins, and we propose a method to identify those proteins for which AF is predictive.