Constrained protein Large Language Model illustrated in protein stability, function and epistasis (opens in new tab)

Our understanding of protein function and evolution is largely based on the relationship between amino acid sequence and overall fold, now effectively captured by computational models. Yet predicting how mutations--shaped by epistasis--alter protein behavior, especially in dynamic or structurally ambiguous regions, remains difficult. Here we present D2D, which combines a self-supervised protein language model with protein-specific evolutionary information to predict mutational effects using l...