Accurate Mutation Effect Prediction using RoseTTAFold

Abstract

Predicting the effects of mutations on protein function is an outstanding challenge. Here we assess the performance of the deep learning based RoseTTAFold structure prediction and design method for unsupervised mutation effect prediction. Using RoseTTAFold in inference mode, without any additional training, we obtain state of the art accuracy on predicting mutation effects for a set of diverse protein families. Thus, although the architecture of RoseTTAFold was developed to address the protein structure prediction problem, during model training RoseTTAFold acquired an understanding of the mutational landscapes of proteins comparable to that of large recently developed language models. The ability to reason over structure as well as sequence could enable even more precise mutation effect predictions following supervised training.