De novo design of miniproteins targeting GPCRs
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E Muratspahić, D Feldman, DE Kim, X Qu…
Nature, 2026
nature.com
G protein-coupled receptors (GPCRs) play key roles in physiology and are central targets for drug discovery and development1, 2, but the design of protein agonists and antagonists has been challenging as GPCRs are integral membrane proteins and conformationally dynamic3–6. Here we describe computational de novo design methods and a high-throughput “receptor diversion” microscopy-based screen for generating GPCR binding miniproteins with high affinity, potency and selectivity. We design miniprotein agonists that …
