Forbes 30U30, ex-CTO @Labstep, ex @DEShawResearch, ex @charmtherapeutx. Currently building frontier open-source co-folding models at @open_fold

London, England
Joined March 2016
Oh yes @open_fold !! Thanks for the mention @kevinace
Six days ago I replied to @bryan_johnson about my cancer vaccine. That reply put my story in front of a lot shit ton of new people. Since then: ~1M impressions, 5.5K profile visits, ~550 replies, and 60+ DM's and emails. The part I didn't expect: a lot of it wasn't well-wishes. It was real help. Jan Domański, a scientist at OpenFold, offered to model my cancer's resistance mutations with AI, for free. Dennis Watson at Travera offered immune testing to track how my vaccine is working. @miriamgonp, a fellow patient, is building her own vaccine path, and we're comparing notes. Thank you, Bryan, and thank you to everyone who reached out. I read every message. If you're someone who wants to help or better yet if I can help you in any way, my DMs are open.
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Jan Domanski retweeted
Today we're sharing an update on our diffusion method from last year, RFdiffusion3, in @ScienceMagazine. Notably, we show significant improvement in design of sequence specific proteases for amyloid sequences and metallohydrolases for pesticide degradation.
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If only these constraints could be cheaply generated experimentally for cases where structure is unknown…
Good afternoon, San Francisco! Today, we're releasing Test-Time Structure-Space Search, a new OpenDDE inference algorithm for more effective co-folding when designing and selecting antibody drug candidates 🧬. 16% → 78%, that's top-1 success on antibody–antigen targets where OpenDDE usually fails, using Test-Time Structure-Space Search with just five correct contacts. Frozen model. No retraining. No gradients through the network. Test-time compute isn't only for LLMs. Rather than only picking the best of many samples, we search for better structures while the sampler is still denoising. Same OpenDDE, same five contacts, same budget of 25 candidates per target: • re-rank with the contacts: 33% • steer the sampling with them: 78% Re-ranking recovers only about a quarter of the gain. The rest comes from changing the sampling trajectory itself. How it works: • At scheduled denoising steps (about three dozen per sample), we check OpenDDE's predicted clean complex against the contacts. • If they fail, a solver moves the antibody as a rigid body: Refine (nudge locally) → Search (broad pose search, only if still failing) → Refine (polish the best pose). • A clash-aware energy refuses moves that create severe overlaps, and fused GPU kernels make thousands of pose evaluations per call practical. • The corrected structure goes back to the sampler. If the contacts already hold, nothing moves. Results: 805 held-out SAbDab targets where the base model usually fails (median DockQ < 0.23 over five samples). Top-1 success by number of known contacts: 0 (unguided): 16% and 5: 78%. With 5 contacts, mean top-1 DockQ goes 0.14 → 0.43 and the CAPRI-medium rate 11% → 39%. Pocket mode (5 epitope residues, nothing on the antibody side): 17% → 33%, versus 26% for re-ranking. A smaller gain, same pattern. Try it: Put contact pairs or epitope residues in the "constraint" field of your input JSON and run with --use_tfg_guidance true. Checkpoints and output format are unchanged, and inputs without a constraint behave as before. With the optional trunk cache, inputs that differ only in their constraint share one trunk. Examples for Fab, Fv and VHH are in examples/tfg. Fine print: Constraints are simulated from reference structures, so they are correct by construction. This measures what accurate interface knowledge is worth, not robustness to experimental noise, and wrong contacts can push success below unguided. SAbDab only. Success = DockQ ≥ 0.23, 25 candidates per target, 95% bootstrap CIs. Validated on one GPU with 200 diffusion steps. Code: github.com/aurekaresearch/Op… Tech Report: github.com/aurekaresearch/Op…
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The blog post is actually quite neat, however in my experience the real boundary remains accuracy and generalization rather than "how fast it produces a structure" – getting an answer faster is good (matters for benchmarking/evaluation) but in a discovery program accuracy is key
Most co-folding models can only reason over a small fraction of biological reality because they hit a wall as structures get larger. Past 4,000 residues, OpenFold3, for example, can no longer evaluate structures. LightFold, Flagship’s proprietary co-folding model, keeps predicting structures up to ~5,400 residues, showing that it’s able to operate in territory that is no longer practical for other models. Read more: flagshiplabs.substack.com/p/…
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My my jaw dropped, then i just fell on the carpet
For almost two years, TT-Bio has been inference only. Starting today, you can also train bio models on @tenstorrent hardware. We're kicking it off with the OpenFold3 architecture, easily adaptable to other architectures. You can train on anything from a single card to multiple Galaxy servers. Training OpenFold3 on a Tenstorrent Blackhole Galaxy already comes close to the performance of an NVIDIA DGX H200, at about a quarter of the cost. This makes training bio models accessible to more people. I hope it leads to new model architectures that take full advantage of the Tenstorrent architecture. Agents make all of this possible. Our software stack is open source, OpenFold3 is too, and agents love both. Big thank you to our @open_fold friends. The fact that OpenFold3 is truly open source made my life so much easier.
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We're excited to be unveiling the first challenge in our protein design competition! EGFR is the target from the first competition, but we're asking for much more this time: a mouse cross-reactive binder that conditionally binds at acidic pH but not neutral pH. This problem is at the frontier of today's capabilities, but I'm confident that the world's leading designers, equipped with a ton of tokens and compute, and over 1,000 designs screened in the lab will be able to solve it.
We're launching Challenge 1 of the Anthropic x Adaptyv Protein Design Competition on @proteinbase: design a conditional binder to EGFR, a key cancer target. The goal: bind EGFR under the acidic conditions of the tumor environment, but not at the normal pH around healthy cells. Moreover, the proteins must bind to both the human and the mouse variant of EGFR to support easier preclinical testing
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Jan Domanski retweeted
🛵 This might just be the lads’ greatest work yet…
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Crazy. One AI guy spent 3 evenings creating an ad for Poland. And its much better than what a full agency produced with a $1.5M budget. Are traditional ad agencies in trouble? Author: sztuczna_polska instagram
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If you're tired of over-hyped TechBio commentary – from people that broadly know nothing about nothing – this is such a good read. Yeah, we didn't break the bank with OpenBind but the wheel of open-source keeps on turning. ahalflife.substack.com/p/ope…
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Okay, let's try that?
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As we build the next generation of biomolecular OpenFold models, we are looking to increase our staffing on both the scientific and engineering fronts. I thought it'd be worthwhile to write down our philosophy and what we're offering, as well as what we're looking for. If this resonates with you, please apply at the link below. What we're offering: True open source: we are contractually obligated by our funding streams to open source everything we do, including our training code infrastructure and training data, which no other group in the space has done. All the results we publish are fully reproducible with no missing "training enhancements" that keep the recipes hidden. We will not become a startup and we will not pivot to an API model. We are doing this exclusively as a public good for the public commons. Of course, commercial companies can and are encouraged to build on top of our models, but you will be contributing to an ecosystem guaranteed to remain open source. Long horizon research: because we are not trying to turn a profit or satisfy investment trends, we can focus on hard problems that commercial labs are disincentivized to tackle. Our research vision spans years, not months, even while we release updates on a quarterly basis. This translates to problems spanning conformational ensembles, novel regions of chemical space, antibodies, nucleic acids, IDRs, macromolecular machines, and more. Reach for the frontier: the open source ecosystem currently lags the industrial frontier by a few years. We aim to eliminate this gap. The two big deltas are engineering expertise and compute resources. We're doing alright on the latter, but it is the former where we need to grow. To make this possible we offer salaries and compute resources competitive with industry. We are looking primarily for types of people, or the intersection of the two! Machine learning scientists and engineers: people who have built and trained models at scale, whose command of the literature extends to the latent developments in efficient diffusion, optimization, recurrence, and reasoning. Bioinformaticians and computational biologists: people who can assemble large and complex heterogeneous datasets, who write efficient data pipelines, and who deeply understand the structural biology domain. If this is of interest to your network, please reshare. And if this interests you directly, please apply using the link below. This link is a catch-all site and so the job description and salary range are generic. It's there to help us streamline collection and review of resumes. opportunities.columbia.edu/j…
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Please do it @AnthropicAI
I hope @AnthropicAI will consider supporting the open source frontier @openfold as a member! We support a few of these tools and others have gone proprietary over the last year
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I hope @AnthropicAI will consider supporting the open source frontier @openfold as a member! We support a few of these tools and others have gone proprietary over the last year
It’s been an absolute privilege teaching Claude how to be a protein designer! By orchestrating open-source protein design and folding models, Claude successfully designed de novo protein binders against 14 of 15 targets, with high success rates and high affinities, as measured by @adaptyvbio and @TwistBioscience. Our results are enabled by multiple landmark innovations in molecular modeling, including, but not limited to: • ESMFold2 and ESMFold2-Fast from @biohub • PXDesign and Protenix v2 from @ByteDanceSeed_ • ipSAE from @RolandDunbrack • RFdiffusion, RFdiffusion3, ProteinMPNN, and SolubleMPNN from @UWproteindesign • FreeBindCraft from @EPFL @AriaxBio • BoltzGen from @boltz_bio • Proteina-Complexa from @NVIDIAHealth • Genie 3 from @ColumbiaSysBio • Caliby and SolubleCaliby from @Stanford • AlphaFold and AlphaProteo from @GoogleDeepMind @IsomorphicLabs
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It’s been an absolute privilege teaching Claude how to be a protein designer! By orchestrating open-source protein design and folding models, Claude successfully designed de novo protein binders against 14 of 15 targets, with high success rates and high affinities, as measured by @adaptyvbio and @TwistBioscience. Our results are enabled by multiple landmark innovations in molecular modeling, including, but not limited to: • ESMFold2 and ESMFold2-Fast from @biohub • PXDesign and Protenix v2 from @ByteDanceSeed_ • ipSAE from @RolandDunbrack • RFdiffusion, RFdiffusion3, ProteinMPNN, and SolubleMPNN from @UWproteindesign • FreeBindCraft from @EPFL @AriaxBio • BoltzGen from @boltz_bio • Proteina-Complexa from @NVIDIAHealth • Genie 3 from @ColumbiaSysBio • Caliby and SolubleCaliby from @Stanford • AlphaFold and AlphaProteo from @GoogleDeepMind @IsomorphicLabs
Many drugs work by binding to a specific target in the body and blocking or changing what it does. An important first step in the drug development process is designing a molecule that can bind tightly to its target. Traditionally, that's meant weeks or months of expert work per target, sifting through a large number of candidates to identify the few that work. We wanted to test if Claude could successfully design novel protein binders from scratch (also called de novo design). With a protein design prompt written by a human expert, Claude autonomously designed protein binders against 14 out of 15 targets. We then worked with Adaptyv Bio and Twist Bioscience, who independently built and tested the proteins Claude designed.
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Lmao
dario's right that most human diseases are solvable in 5-10 years, but nobody has done the thinking on how: - biologists especially are sooo lost in the details. it's better to not learn biology at all than to learn the standard version, our understanding is that far off - injecting dumb drugs into a system this complex is the wrong level of abstraction - we should be taking @drmichaellevin far more seriously. the cells already know how to build things, we just don't know how to talk to them
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Today it's time for me to build my 1st ever game, welcome to Gaiofana Express 🏃 gaiofana.it/hack/en Built in Italy ☕
🤖 Made with AI
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New from me: Young people in Britain are some of the most well-educated in the rich world, but economic stagnation means that breeds not growth but frustration. In fact, US workers who are functionally illiterate now earn roughly the same per hour as the average British worker.
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MS products... every single time, i need to interact with this it's just levels of nonsense that make me scream. needlessly complicated, slow, fragmented, cluttered. why?
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