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Computationally design de novo toxin-neutralizing proteins with deep learning

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Use deep-learning protein design (RFdiffusion) to computationally create small, ultra-stable proteins that bind and neutralize conserved venom toxins, manufacturable cheaply by microbial fermentation without animal immunization — as low-cost broad-spectrum antivenom components o…

Institute for Protein Design / Baker Lab (University of Washington, HHMI); Technical University of Denmark (Laustsen, Jenkins); Liverpool School of Tropical Medicine (Casewell); University of Northern Colorado (Mackessy) · Global

Using the deep-learning method RFdiffusion (with ProteinMPNN sequence design and AlphaFold2 filtering), researchers de novo designed small (~100-amino-acid) proteins to bind three-finger toxins from elapid venom: short-…

Short-chain neurotoxin binder (SHRT): mouse survival vs 3× LD50 challenge100% (incl. 15-min post-toxin rescue)
Long-chain neurotoxin binder (LNG): mouse survival vs α-cobratoxin100% (preincubation & 15-min rescue); 60% at 30-min rescue

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Arnaud Gissinger

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