Designer miniproteins target GPCRs with high precision

Nature reports computational de novo design of miniproteins that bind G protein-coupled receptors (GPCRs) with high affinity, enabling both agonists for itch/pain receptors and antagonists for cancer, metabolic disorders, and migraine. Cryo-EM structures of five receptor–miniprotein complexes closely match the design models, validating the approach, and a designed chemokine receptor antagonist mobilizes hematopoietic stem and progenitor cells in vivo with fewer adverse effects than a clinically used drug.