Assistant Professor at the University of Zurich. 🖥️ protein design, machine learning🤖, crystallography💎, cryoEM🔬. Anti-theist. Avid weirdness connoisseur 🎩

Zurich, Switzerland
Joined December 2018
ʙɪɴᴅᴄʀᴀꜰᴛ2 is out, and we're not waiting for the paper. The full code drops today, free for academic and industry use. We're releasing it early so you can start designing right now, and bring its full power to the current Adaptyv competition. github.com/PacesaLab/BindCra…
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The target for challenge 4 is TfR1! Binding, mouse cross-reactivity, and pH-sensitivity.
Challenge 4 of the Anthropic × Adaptyv Protein Design Competition on @proteinbase is open: design a pH-sensitive protein to help shuttle drugs into the brain. TfR1 is a receptor protein that brings iron-loaded transferrin into cells. It is highly expressed in the blood-brain barrier and drug developers can use this receptor to get drugs to pass the blood-brain barrier. The drug is fused to a binder to TfR1, which makes cells absorb the protein complex. If the binder is pH-sensitive it will release from the receptor inside the endosome and then exit the cells on the brain-facing side to deliver the therapeutic into the brain. In this challenge, the goal is to make a pH-sensitive binder to TfR1 that targets precisely the right region on the receptor in order to allow absorption into the cell.
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BindCraft2 v1.0.4 has been released: with significantly improved VHH, scFv, ARP, and induced fit targeting. WE also improved speed and code stability. Try your difficult campaigns again. Great work by Erik Mäeots, Leonardo Tredese and Elizaveta Chernova.
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@bradyajohnston this is showing off the new Molecular Nodes agent friendly API
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Martin Pacesa retweeted
The cool thing about the Fold'EM paper, which directly uses images of EM particles as inputs for diffusion guidance, is that in principle it can be ported over to a codesign model like BoltzGen for modeling display/immunization-derived antibodies that have never been sequenced
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Slop PDB incoming
Announcing a New Beta MCP Server: Connect AI agents to RCSB PDB APIs and PDB data Please try it out and let RCSB PDB know what you think... rcsb.org/news/6acfa3d74ec378…
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Martin Pacesa retweeted
Are scientists still here? Ones that aren’t complaining about academia but are engaged? If so, new work from the lab that is pioneering in more ways than one. A tour de force of protein biochemistry and biophysics focused on the tight junction system. 🔗biorxiv.org/content/10.64898…
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of course that's your contention. you're a first-year frontier bio guy. you just finished reading about CRISPR, probably watched a Doudna talk too. so now you're convinced everything is just gene editing. that's gonna last until next month when you discover base editing, and then you're gonna be talkin' about how cutting DNA was barbaric and double-strand breaks are a legacy approach. then you're gonna read about delivery, and suddenly everything's about lipid nanoparticles and how editing was the easy part and the whole goddamn thing is bottlenecked by getting it to the right organ. that'll last until somebody shows you AlphaFold, and then you're gonna be in here regurgitating DeepMind, talkin' about de novo enzymes and virtual cells and how wet labs are economically obsolete. then six months from now you'll watch one assay fail four times in a real lab, and start telling everybody the bottleneck was never ideas, it's validation. somewhere in there you'll find a guy named Keith on Telegram, and you'll start doing reconstitution math in your head at dinner. and by next year you're gonna be standing right here explaining to me you reversed your biological age by six years because you picked the clock that said so.
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Don’t look at my CV
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Martin Pacesa retweeted
Bacteria have immune systems to defend against their viruses. This animation shows the proposed mechanism of the Zorya defense system from our work with @NMITaylorLab: a proton-driven membrane complex related to the bacterial flagellar stator. doi.org/10.1038/s41586-024-0…
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Martin Pacesa retweeted
Terance Tao: Imagine prescribing a drug no one understood. Medical community:
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The first Bindcraft2 hits already working in real life. Thats some quick turnaround time for the labs.
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Anyone else seen this? CryoEM models without any volume reconstruction. Straight from the micrographs, inferred structures restrained by the actual particle data. So sequence + limited particles = structure?! Bypassing all that time making a map just to still model after
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A universal predictive model of the cell would dramatically accelerate science, allowing biologists to perform experiments digitally. Today we’re announcing a major partnership with the DOE and NIH. The goal of this partnership is to generate the data that will be needed to build an accurate model of the cell with artificial intelligence. Isomorphic, Google DeepMind, and Meta are joining us as founding partners in the Virtual Biology Initiative. This is the beginning of a large scale coordinated effort to map cellular biology to power the development of digital models of life. Other leading scientific institutions and consortia including the Allen Institute, Broad Institute, Gladstone Institutes, the Human Cell Atlas, the Human Protein Atlas, the Wellcome Sanger Institute, as well as NVIDIA, are working together as part of this international scientific project. Creating a predictive model of the cell is one of the most important challenges for the next decade of science. The insights that come from this could unlock a far greater understanding of disease, and open new paths for cures. We invite the worldwide scientific community and other funders to join us in this effort.
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TNFα is the target for our second challenge! This target is tough on its own for binder design and the pH requirement ups the difficulty even more. Good luck to all participants!
Announcing Challenge 2 of the Anthropic x Adaptyv Protein Design Competition! Humira, the best-selling drug ever, blocks TNF-α, an inflammation marker protein that’s overexpressed in rheumatoid arthritis and Crohn’s disease. In this challenge, the goal is to make a better binder for TNF-α that also releases selectively at pH 6.0 in the endosome of cells to improve drug half-life. The protein must also bind both human and mouse TNF-α, making it easier to test the same design in preclinical models.
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Martin Pacesa retweeted
Would encourage companies making big announcements to release preprints so that the larger community can provide them real peer review so as to avoid silly claims printed in stone in overpriced glam journals.
Biosecurity is too important for security theater. In a quick test with Raygun, we found that DeepMind's SynthIDBio watermark signal could be washed out while preserving the predicted structure. We don’t think protein sequence watermarks buy much biosecurity.
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too many possibilities for molecular replacement (20 domains all same fold) + aniso diff 5A / 2.5A + 60% solvent. not profoundly surprising but much smoother experience than any available single software. prompt. density. structure. with a side of dashboard.
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Martin Pacesa retweeted
The Ariax agent is definitely the easiest and now possibly the cheapest way to generate binders!! And it has BindCraft2. Anthropic competition enjoyers take note!
Ariax goes agentic. The best protein designer is already on your computer. Give Codex, Claude Code, or your preferred agent hosted protein-design tools and engine-specific skills with the Ariax CLI. ariax.bio/resources/ariax-ap…
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Absolutely loving the automated mass photometer from Refeyn
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Martin Pacesa retweeted
Replying to @SakanaAILabs
(Schmidthuber invented the name Sakana 1387)
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Martin Pacesa retweeted
Ariax goes agentic. The best protein designer is already on your computer. Give Codex, Claude Code, or your preferred agent hosted protein-design tools and engine-specific skills with the Ariax CLI. ariax.bio/resources/ariax-ap…
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