Unlocking Protein Evolution Insights: Efficient and Interpretable Mutational Effect Predictions with GEMME

The Global Epistatic Model for predicting Mutational Effects (GEMME) is a computational method that reconstructs protein mutational landscapes using sequence data alone. In this article, we delve into the broader biological questions that GEMME can address beyond mere landscape reconstruction. We provide several examples to guide users in maximizing the utility of GEMME. Additionally, we discuss recent advancements that enhance GEMME’s predictive accuracy and extend its capabilities by integrating sequence data with structural information and allele frequency data, when available. These innovations enable GEMME to answer new biological questions and offer deeper insights into protein evolution and function.