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Joseph Watson
@_JosephWatson
Co-Founder @ Xaira Therapeutics Former Baker Lab PostDoc at @UWproteindesign. Interested in generative modelling for molecular design. Views my own.
Joined September 2020
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    I’m excited to share our significantly-updated preprint on de novo antibody design, where we now demonstrate the structurally accurate design of scFvs (in addition to VHHs) with RFdiffusion! biorxiv.org/content/10.110…
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    DALL-E’s amazing images are popping up all over the web. That software uses something called a diffusion model, which is trained to remove noise from static until a clear picture is formed. Turns out diffusion models can design proteins too!
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    Replying to @_JosephWatson
    Today we’re sharing a deep-learning method for protein design called RoseTTAFold Diffusion. With minimal input, it turns prompts (“create a molecule that binds X”) into new proteins that fold and function in the lab. We’ve tested 100s already. PDF here: bakerlab.org/2022/11/30/dif…
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    We’re really happy to share our preprint demonstrating the atomically-accurate design of single-domain antibodies (VHHs) with RFdiffusion!
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    We’re really excited to announce that we’re releasing code for running RFdiffusion! The code is released under an open source license and is free for anyone to use.
    Today we're making RF Diffusion, our guided diffusion model for protein design with potential applications in medicine, vaccines & advanced materials, free to use. The software has proven much faster and more capable than prior protein design tools. bakerlab.org/2023/03/30/rf-…
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    Replying to @_JosephWatson
    The code is available both to download from GitHub, and also, thanks to the wonderful @sokrypton, as a Colab Notebook. github.com/RosettaCommons… colab.research.google.com/github/sokrypt…
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    It's so great to see our RFdiffusion paper now live @Nature. This article from @ewencallaway gives a great overview of RFdiffusion and protein diffusion models more broadly, and also highlights some of the ways people are already using it in their own research!
    Digital art techniques can now devise custom, working biomolecules on demand. These proteins could form the basis for vaccines, therapeutics and biomaterials. Read the full story: nature.com/articles/d4158…
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    I'm excited to announce that I'm part of the team at Xaira Therapeutics! This project has been some time in the making. I'm convinced that generative modelling, and ML for biology more generally, will play a pivotal role in the next generation of therapeutics. 1/2
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    Replying to @_JosephWatson
    We designed binders to five medically-relevant molecules. These binder proteins pass our most stringent in silico metrics and we’re testing them in the lab right now. In the future, it might only take a few seconds to design a high-affinity binder protein for any target you want
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    Such a nice article from @ewencallaway @Nature - thanks so much for writing it!! ‘A landmark moment’: scientists use AI to design antibodies from scratch
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    Replying to @_JosephWatson
    RFdiffusion is best-in-class for protein backbone generation (low RMSDs to AlphaFold models) and surpasses inpainting and hallucination at scaffolding functional motifs. It makes bigger, more diverse, and more accurate proteins. (600aa protein, gray=design, colors=AF2)
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    Replying to @_JosephWatson
    RFdiffusion can also be guided with symmetry. For example, we have designed and are characterizing a new protein that engages all three symmetric ACE2 binding sites on the SARS-CoV-2 spike protein. In this case C3 symmetry works, but any symmetry is possible.
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    We said last week we were excited to see RFdiffusion being tested in the wet lab. Today, the paper is on @biorxivpreprint, and there's a LOT more exciting experimental data! See David's thread below 👇
    We’re very happy to announce that our RFdiffusion manuscript is now on bioRxiv! A lot can change in a week - we’ve now tested over a thousand designs and there’s so much exciting new data! 🧵
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    Replying to @_JosephWatson
    Not to mention all the symmetric oligomers @HelenEisenach and @andrewjborst have designed and tested in the lab! Being able to design with any symmetry you want opens up so many applications for therapeutics and enzyme design.