Sailan Shui, Pablo Gainza, Leo Scheller, Che Yang, Yoichi Kurumida, Stéphane Rosset, Sandrine Georgeon, Raphaël B Di Roberto, Rocío Castellanos-Rueda, Sai T Reddy, Bruno E Correia
Small-molecule responsive protein switches are crucial components to control synthetic cellular activities. However, the repertoire of small-molecule protein switches is insufficient for many applications, including those in the translational spaces, where properties such as safety, immunogenicity, drug half-life, and drug side-effects are critical. Here, we present a computational protein design strategy to repurpose drug-inhibited protein-protein interactions as OFF- and ON-switches. The designed binders and drug-receptors form chemically-disruptable heterodimers (CDH) which dissociate in the presence of small molecules...
October 1, 2021: Nature Communications