Guiding discovery of protein sequence-structure-function modeling

Protein engineering techniques are key in designing novel catalysts for a wide range of reactions. Although approaches vary in their exploration of the sequence-structure-function paradigm, they are often hampered by the labor-intensive steps of protein expression and screening. In this work, we describe the development and testing of a high-throughput in silico sequence-structure-function pipeline using AlphaFold2 and fast Fourier transform docking that is benchmarked with enantioselectivity and reactivity predictions for an ancestral sequence library of fungal flavin-dependent monooxygenases.