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
Jan Domanski retweeted
We’re at the AI Drug Discovery Development Summit in Boston, Oct 27–29. Come find us at booth #8. On Oct 28 at 9:30 a.m. ET, @jianwen_xie and @jandom_random of @open_fold take the main stage to talk about open-source model training for drug discovery. First up, fine-tuning OpenFold3 and training it on synthetic data. Then a look at how Lambda’s infrastructure speeds up that fine-tuning, with a deep dive into TurboPairFormer, a fast, stable GPU kernel built for OpenFold3 training.
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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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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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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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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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Jan Domanski retweeted
Catching skin cancer early is a home robotics problem. Melanoma is highly treatable when detected early, yet today’s screening process depends heavily on patients noticing tiny changes across their entire skin surface. This requires patients to solve a near-impossible visual-memory and registration problem. I built OpenDerm, an open-source 4-DOF robot that captures high-resolution images of the skin and uses them to reconstruct and track the skin surface in 3D over time. The best way to make skin screening truly routine is to bring it into the home. OpenDerm shows that inexpensive robotic skin imaging is possible, but the path to scale is not a dedicated screening robot in every household—it is to make skin screening one of the many useful things a general-purpose home robot can do. Read more about why I built OpenDerm and how it works here: Blog: marionlepert.github.io/blog/… Project: openderm.github.io/
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Did you know that you can run OF3-p2 @open_fold for free with zero setup at portal.openfold.omsf.io/? Try different models and different model weights as they come out. Load protein, DNA, RNA, small molecule, all easy, built by @jandom_random
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Onze voorstellen nieuw Eurobiljet
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Jan Domanski retweeted
Time for another round of binder design
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Jan Domanski retweeted
Yes, you read that correctly: the majority present voted _against_ chat control. But due to the absurdly undemocratic, illegal, procedure they're using, it comes into law anyway after being rejected multiple times before in previous votes. Insane.
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Biomolecular structure prediction is a full-stack challenge, not just a model benchmark. See how NVIDIA accelerates structure prediction with GPU MSA search up to 177× faster, OpenFold3 inference up to 4× faster on NVIDIA Blackwell GPUs, and Fold-CP scaling to 32,000-token complexes across 64 NVIDIA B300 GPUs, composed into agentic workflows with BioNeMo Agent Toolkit. 🧬 Read the full blog nvda.ws/4yfAn2o
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Jan Domanski retweeted
Replying to @Nicolas_Colin
I think the pity and mockery stems from so many Europeans (usually institutions/"experts") dismissing AC's utility. The vast majority of the debate is not over the mechanics and logistics of deployment, but whether widespread AC is in principle desirable in the first place. I think it garners so much attention from Americans (and Europeans such as myself) because it's a vivid distillation of the self-destructive "degrowth" hysteria that is so prevalent and harmful in many European policy matters. It is the same impulse that led to Germany decommissioning its nuclear capacity, and it is a substantial contributor to the broader economic challenges of the continent.
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Jan Domanski retweeted
🍹Weekend project: I (with help from claude - budget $40), was able to get OpenFold3 weights running inside AlphaFold3 codebase (jax). Works for proteins, ligands, rna/dna (1/3)!
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Jan Domanski retweeted
The bitterist lesson
No scaling laws for single-cell foundation models: when bigger atlases stop teaching the model anything In language and vision, the recipe has been simple: more data, bigger models, better performance. Single-cell biology borrowed that playbook. Foundation models for transcriptomics jumped from 1 million cells to atlases of over 100 million, on the assumption that scale would unlock the same gains. Alan DenAdel and coauthors put that assumption to the test, and the result is sobering. Working from a 22.2-million-cell corpus, they pretrained 400 models across five architectures (from PCA and a variational autoencoder up to the Geneformer transformer) and ran 6,400 evaluation experiments. They varied not just dataset size (1% to 75%) but also diversity, using cell-type re-weighting and geometric sketching to deliberately enrich rare cell types and transcriptional states. The finding: performance saturates almost immediately. On cell-type classification, batch integration, and perturbation prediction, most models hit their ceiling at roughly 1% of the corpus, about 200,000 cells. Beyond that, adding millions more cells changed essentially nothing. More diversity didn't help. Even spiking in genome-scale Perturb-seq data, to give the models perturbed phenotypes rather than just healthy ones, failed to move the needle. Larger models did score better overall, but they too plateaued early on data. Two points stood out. Simple baselines (PCA, logistic regression) often matched or beat the transformers. And the strongest model, SCimilarity, won not because of size but because its contrastive training objective is aligned with the downstream task. For single-cell data, what you train on and how you frame the objective matters far more than how much you collect. This reframes a quiet but expensive habit. In drug discovery, biotech, and any pipeline leaning on cell atlases, the instinct to keep scaling pretraining corpora may be burning compute for no return. The real leverage sits elsewhere: curating high-quality, task-relevant data and matching the training objective to the actual question you're trying to answer. Paper: DenAdel et al., journal license | doi.org/10.1038/s41592-026-0…
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