Design of a Protein with Improved Thermal Stability by an Evolution?Based Generative Model

Efficient design of functional proteins with higher thermal stability remains challenging especially for highly diverse sequence variants. Considering the evolutionary pressure on protein folds, optimizing fitness could help designing folds stability. Using a generative evolution model trained to capture variation patterns in natural sequences, we designed artificial sequences proteinaceous inhibitor pectin methylesterase enzymes. These inhibitors have considerable industrial interest avoid phase separation fruit juice manufacturing or reduce methanol distillates, averting chromatographic passages triggering unwanted aroma loss. Six out seven designs up 30 % divergence other are and two improved This method can improve expanding space, traits valuable applications scientific research.