Claude Scorpion Toxin Binder Design

How Claude designed protein binders against scorpion neurotoxins \ Anthropic Skip to main content Summary: As part of our work experimenting with how Claude can help accelerate drug discovery, we asked an internal research model to design minibinders (small proteins that attach tightly to a target) against scorpion neurotoxins. Claude worked from our prompt and four follow-ups, which we developed in collaboration with the financial investment research firm Citrini Research. Teams at Adaptyv Bio and Twist Bioscience experimentally tested 211 designs for binding. Of these, 17 met our criteria. We’re releasing all 211 designs and their data as a resource for the field.

In August, we showed how Claude designed protein minibinders after being given a single prompt. A month before we released those results, a team from Citrini Research had approached us with an interesting question: could Claude (and AI drug discovery more generally) enable a group of motivated nonexperts to tackle a genuine problem in human health? Members of our life science research team set out to answer this, first by brainstorming problems with Claude. We landed on asking for Claude’s help designing novel protein binders against scorpion neurotoxins, with the hope that they could one day be used to develop a scorpion antivenom. Scorpions sting 1.2 million people or more every year, resulting in more than 3,250 deaths, mostly among children in parts of the world with limited access to medical care. New treatments are expensive to make, and are also unlikely to earn back the cost of developing them. With so little investment, scorpion envenomation has been described as a neglected tropical disease. We started by giving Claude the same prompt we’d used in our earlier protein-binder study, after modifying it with Citrini. 1 Over the next 64 hours, an internal research model, operating within Claude Science, worked mainly autonomously, although we directed its work with four follow-ups. Under our supervision, Claude analyzed the research data, generated the figures, and drafted the final report. Claude’s design campaign produced 17 protein binders that each bind to one of four scorpion neurotoxins that are known to be dangerous to humans. Throughout the process, Claude generated 318,484 protein designs and selected 180 of them for testing. Our team added 31 more, with Claude’s help. Our partners at Adaptyv Bio and Twist Bioscience, two contract research organizations (CROs), lab-tested all 211 designs to see if they would bind to the toxins they were designed against, and 17 designs met our criteria for a binder. We have not confirmed whether these binders neutralize scorpion venom in a cellular environment, so we do not claim to have produced an antivenom. We sent Claude’s work to two outside experts, Susana Vázquez Torres and Timothy P. Jenkins, who said they felt this work was a promising first step. If AI can now design credible binders against several hard-to-target toxins in days and they can be confirmed in the lab within weeks, this could, in theory, speed up discovery for envenomation and other neglected diseases. The challenge, as always, is turning those binders into safe, affordable, and widely accessible drugs. We share more detail in our technical report , and are making all 211 designs and their data available . Designing a binder against almost any target no longer seems unrealistic. We can now obtain very tight binders remarkably quickly, and binding itself is no longer the main bottleneck. For venomous animals such as snakes and scorpions, whose bites and stings kill or seriously injure large numbers of people, particularly in underserved regions, the real impact will come from tackling the parts of the therapeutic pipeline that go beyond binding. The challenge is to use these extraordinary tools to develop molecules that can become real drugs, ones that are safe, affordable, and widely accessible.

Susana Vázquez Torres , Postdoctoral Researcher, Structural Biology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. Designing de novo binders against five toxins from four species of scorpions Scorpion venom contains multiple protein neurotoxins. The neurotoxins that are most likely to harm or kill humans attach to sodium channels , large proteins embedded in the membranes of nerve cells that allow them to fire. When sodium channels are disrupted, nerves fire at the wrong time—this releases large amounts of stress chemicals, like adrenaline. In severe cases, this can cause heart failure and excess fluid buildup in the lungs, occasionally resulting in death. There are some antivenoms available for scorpion stings. They’re generally made using the antibodies of immunized animals, a process that can take months. Venom is milked from thousands of scorpions and used to immunize horses; scientists then purify the resulting antibodies from the horses’ blood. Traditional antivenoms can work when given early, but they’re usually effective for only a small number of neurotoxins. They’re also expensive to produce, and in many regions are costly or in short supply. De novo design offers a potential solution. A binder is a molecule that attaches tightly to a specific target; antibodies are one natural example. In principle, a binder that targets the part of a neurotoxin that latches onto sodium channels could stop the toxin from reaching the channel. In de novo design, protein binders are generated from scratch against a specific target. These binders are designed computationally and can be optimized for druglike properties such as potency and stability, which could make them easier to supply in regions where stings most often occur. Our approach was inspired by an earlier effort that designed de novo proteins that neutralized snake neurotoxins and protected mice. To our knowledge, no de novo -designed binders against scorpion neurotoxins have been described. For this campaign, we chose to target five scorpion-venom neurotoxins across four regions: Mexico (Cn2), Brazil (Ts1), North Africa (AaH I and AaH II), and the Middle East (LqhIII). We also chose to aim the designs at each toxin’s channel-binding site. Claude picked the toxin structures to use for design by searching the Protein Data Bank (PDB) as well as the AlphaFold database (AFDB). For each toxin, it selected five hotspots , specific amino acid positions on the toxin that its binder designs were meant to latch onto.

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