I'm excited to announce some major updates to our ProteinEBM paper with Chenxi Ou @sokrypton.org!

New OpenFold3 preview out! (OF3p2) It closes the gap to AlphaFold3 for most modalities. Most critically, we're releasing everything, including training sets & configs, making OF3p2 the only current AF3-based model that is functionally trainable & reproducible from scratch🧵1/9

On the nature of the earliest known lifeforms

Five years ago, we released FLIP. The core question was: can ML models for protein fitness prediction generalize in the ways that actually matter for protein engineering, i.e. low data, extrapolation to more mutations, out-of-distribution sequences?

New pre-print from the lab on scaling transferable implicit transfer operators to protein dynamics. Collaboration with @olewinther.bsky.social lead by @panosantoniadis.bsky.social.

Introducing The Structural History of Eukarya (SHE): The first proteome-scale phylogeny constructed entirely from 3D structure. We computed 300 trillion alignments across 1,542 species to map the tree of life. 🧵👇 (1/5)

While most AI models are trained on text and images, the Polymathic AI collaboration has something different in mind: AI trained on #physics: https://www.simonsfoundation.org/2025/12/09/these-new-ai-models-are-trained-on-physics-not-words-and-theyre-driving-discovery/ #science

New Preprint!! We show that binding entropy can be quantitatively predicted from crystallographic ensemble models, accounting for both protein conformational entropy and solvent entropy! www.biorxiv.org/content/10.6...

FoldMason is out now in @science.org. It generates accurate multiple structure alignments for thousands of protein structures in seconds. Great work by Cameron L. M. Gilchrist and @milot.bsky.social. 📄 www.science.org/doi/10.1126/... 🌐 search.foldseek.com/foldmason 💾 github.com/steineggerla...

Important perspective from Greenland.

UK Research and Innovation, plus its research councils, quietly quit X. Via @robinbisson.bsky.social @sophieatrpn.bsky.social www.researchprofessionalnews.com/rr-news-uk-r...

I found the secret Pret at Heathrow Terminal 5

This was fun work and a remarkable effort across the computational and wet-lab teams! Strategies for in-silico filtering and ranking of antibody designs have been under-discussed in the literature, e.g. in most technical reports on antibody design that I've seen. Let's talk about these here! [1/n]

At Absci, we performed de novo antibody design campaigns against "zero-prior" epitopes—lacking structural data from antibody-antigen or protein-protein complexes. Model architectures, training data curation, and scoring protocols are fully described. Preprint: www.absci.com/wp-content/u...

GERMAN PRESIDENT STEINMEIER: “.. the United States has broken with the values that it helped to establish .. “.. we have now moved beyond the stage where we can lament the lack of respect for international law or the erosion of the international order; we are far beyond that, I believe.”

Recently found out about @jvkersch.bsky.social's `tmtools` github.com/jvkersch/tmt.... It works nicely! Being able to pass user-defined sequence alignments is a nice (if simple) feature that is missing from OpenStructure's own `tmtools` @torstenschwede.bsky.social.

Black swan moment for energy production and storage?

🏛️ 🔍 👀 "There are no optical corrections in the Parthenon"

Visiting Ephesus at #embointegmod25 to look for the missing AlphaFold 3 code

Would you like to come to my lab for a postdoctoral position? Apply for the EPFL AI Centre fellowship: epfl.ch/research/fun.... FYI, I have funding (ERC & Simon's collaboration) also for 1-2 top candidates who will not secure the fellowship. Same for @krzakalaf.bsky.social lab.

💥 We are *also* organizing Machine Learning for Structural Biology @ EurIPS, Copenhagen!! Topics include anything in the ML+bio intersection. Submit your ML+bio short papers! Authors can even present in both locations if they have people in both locations 🚀

Cool-looking work by @piompons.bsky.social @albecazzaniga.bsky.social @fra-cutu.bsky.social, going beyond existing works on sampling different conformational ensembles with AF2.

Recently tested some de-novo minibinders against two targets (thanks Adaptyv!) designed using our open-source design library, `mosaic`; our best method got hit rates of 7/10 and 8/10 and affinities as low as single-digit nanomolar. Wrote up some thoughts here: blog.escalante.bio/minibinder-d...

Posts about research on Bluesky receive substantially more attention than similar posts on X, formerly called Twitter go.nature.com/45Ftiw4

Two exciting openings with us! 🤖🧬🆎🧫💉 - AI Scientist 👉 lnkd.in/eDXHH4E8 - AI Scientist, Drug Creation 👉 lnkd.in/eEvGyaTR You'll work on antibody sequence/structure design, antibody-antigen co-folding, antibody-antigen binding prediction, physics-based methodologies, and more! DMs welcome!

🎉 Excited to share that the last paper of my PhD is now published in PRX Life! We introduce RAG-ESM, a retrieval-augmented framework that makes pretrained protein language models (like ESM2) homology-aware with minimal training cost. 📄 Paper: journals.aps.org/prxlife/abst...

@cyrilmalbranke.bsky.social is 🦋! "ProteomeLM significantly outperforms DCA in recovering experimentally validated interactions. In H. sapiens, ProteomeLM achieves an AUC of 0.83, compared to 0.73 for DCA. Among the top 10 million scored pairs, it recovers 50% of known PPI, versus only 20% for DCA"

A no-miss opportunity to join EPFL. We are a vibrant (had to use it 😉) community working in all branches of basic sciences and engineering, and interdisciplinary studies are strongly encouraged. If you want more information, contact the committee heads, or feel free to DM me. tinyurl.com/bd27ky7p

"When even the most benign activities are subject to capricious disruption and political interference, the luxury of disengagement is no longer a viable option."

AtomWorks is out! Building upon @biotite_python, we built a toolkit for all things biomolecules and trained RF3 with it. All open-source, test it via `pip install atomworks`! AtomWorks: github.com/RosettaCommo... RF3: github.com/RosettaCommo... Paper: tinyurl.com/y2w4z65b 1/6

From social media apps to bank loans and hiring/firing decisions to search engines and shopping sites, are you tired of living a life ruled by opaque algorithms? Pre-order now to Take Back Control on August 5. bit.ly/4idpeGr

Excited to share work with Zhidian Zhang, @milot.bsky.social, @martinsteinegger.bsky.social, and @sokrypton.org biorxiv.org/content/10.1... TLDR: We introduce MSA Pairformer, a 111M parameter protein language model that challenges the scaling paradigm in self-supervised protein language modeling🧵

Our development of machine-learned transferable coarse-grained models in now on Nat Chem! doi.org/10.1038/s415... I am so proud of my group for this work! Particularly first authors Nick Charron, Klara Bonneau, Aldo Pasos-Trejo, Andrea Guljas.

Proved that the diabolical Einstein field equations can be formulated as a well-posed initial value problem, paving the way for huge progress in mathematical general relativity that continues to this date. Goodbye, Madame Choquet-Bruhat

#Postdoc opportunity in #protein #evolution at #EPFL I can highly recommend working with Anne-Florence Bitbol! You'll bounce ideas off a world-class scientist with an awe-inspiring range of interests and a sharp mind—without sacrificing quality of life or a lake view. tinyurl.com/ProteinPostdoc

French scientist denied US entry after officers find phone messages criticizing Trump

Bluesky is the place for science.

Go Sweden! 🇸🇪

🚨 Check out DrugFlow, our new generative model for structure-based drug design. DrugFlow provides an atom-level confidence score for each designed molecule, and can adjust molecular size on the fly! Additional details in thread 🧵 #ICLR2025

Thank you @seanmcarroll.bsky.social: x.com/seanmcarroll.... This has an effect. People want to keep hearing from you and they too will migrate here.

Dear US colleagues, In response to the Trump administration, my university @univ-amu.fr is setting up a new program dedicated to welcoming American scientists wishing to pursue their work in France. There are several M$ in the budget. www.univ-amu.fr/en/public/ac...

Hello American friends here. Please consider making gigantic protests great again. This platform is too small. A centralized app for coordination seems a good idea to me.

POV >Be Ettore Majorana >Discover neutron-proton model of nucleus and predict the neutron first but refuse to publish > Quantize complex scalars but refuse to publish >Predict new kind of fermion >Show possibility of particles with arbitrary spin >Quit physics at 32 >Refuse to explain >Leave ⚛️🧪

Excited to share PoET-2, our next breakthrough in protein language modeling. It represents a fundamental shift in how AI learns from evolutionary sequences. 🧵 1/13

Can we learn protein biology from a language model? In new work led by @liambai.bsky.social and me, we explore how sparse autoencoders can help us understand biology—going from mechanistic interpretability to mechanistic biology.

Back from a short and intense #NeurIPS2024. I enjoyed meeting old friends and catching up with cutting-edge research! I am proud of my team (LIAC at EPFL) with 3 spotlights out of 6 accepted workshop contributions. If you want to join the team, please apply below (deadline December 20th). #chemsky

AlphaFold3 still tends to overfit regions that AF2 multimer predicts to be disordered. Almost all disordered regions become helices in AF3.

Early December, the CASP16 Meeting was held in the Palladium resort in Punta Cana, Dominican Republic. Nick Grishin, myself, and Qian Qong presented the assessment of the monomeric structure predictions, the assembly predictions and of monomers in their oligomeric context. 1/n

Had an awesome time walking among giant ancient trees with a great group of people @neuripsconf.bsky.social. Highly recommended!