On 08 March 2022, the journal BioDesign Research published a review article titled "What Have We Learned from Design of Function in Large Proteins?" by Olga Khersonsky and Sarel J. Fleishman. The article proposes an evolution-guided atomistic design approach that eliminates mutations that could destabilize proteins, induce misfolding, or distort the active site domain of residues, and preserves non-ideal key sequences and structural features through the use of natural backbone and sequence constraints.