📢 We’re launching Proteina-Complexa — and after the Jensen keynote mention, we definitely had to post this thread now ;)
Atomistic binder design with generative pretraining + test-time compute, plus large-scale wet-lab validation.
Project page: research.nvidia.com/labs/genair/...
🧵 1/n

AlphaFold database has entered the era of complexes. Together with NVIDIA, DeepMind and EBI, we use ColabFold, OpenFold and MMseqs2-GPU to predict ~31 million complexes (homo & hetro-dimers) resulting in 1.8 million high-quality predictions
📄 research.nvidia.com/labs/dbr/ass...
🌐 alphafold.ebi.ac.uk

🚨🚨🚨 My institute, the @i2bcparissaclay.bsky.social in beautiful Gif-sur-Yvette and part of @univparissaclay.bsky.social, is recruiting group leaders!
Announcement here:
www.i2bc.paris-saclay.fr/join-i2bc/te...
Open to early career scientist from anywhere or mid-career already in France. Please RB!

A non-catalytic role for RFC in PCNA-mediated processive DNA synthesis The RFC clamp loader remains associated with PCNA beyond the loading step, supporting processive DNA replication by stabilizing the inherently unstable PCNA-polymerase ẟ complex.

Now online! A non-catalytic role for RFC in PCNA-mediated processive DNA synthesis

Multiple protein structure alignment at scale with FoldMason Protein structure is conserved beyond sequence, making multiple structural alignment (MSTA) essential for analyzing distantly related proteins. Computational prediction methods have vastly extended ou...

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...

A tripartite protein complex promotes DNA transport during natural transformation in Firmicutes | PNAS Natural genetic transformation is a conserved mechanism of bacterial horizontal gene transfer, which is directed entirely by the recipient cell and...

Pleased to share our recent article in PNAS - a collaboration with @jessicaandreani.bsky.social & Pablo Radicella, with important roles played by many members of each team.

A tripartite protein complex promotes DNA transport during natural transformation in Firmicutes www.pnas.org/doi/10.1073/...

New paper alert 🚨
I am super happy about it, for many reasons!
👥 It was a great collaborative project with Calum @chgjohnston.bsky.social and J. Pablo Radicella, designed a long time ago (in the pre-AlphaFold era - can you imagine?) together with @polardlab.bsky.social and @raphguerois.bsky.social

How do new centromeres evolve while staying compatible with the division machinery?

Discover it in our new Nature paper! We show centromeres transition gradually via a mix of drift, selection, and sex, reaching new states that still work with the kinetochore.

👉 doi.org/10.1038/s41586-025-09779-1

Structural basis for fork reversal and RAD51 regulation by the SCF ubiquitin ligase complex of F-box helicase 1 pubmed.ncbi.nlm.nih.gov/41256537/ #cryoEM

Proteome-wide in silico screening for human protein-protein interactions Protein-protein interactions (PPIs) drive virtually all biological processes, yet most PPIs have not been identified and even more remain structurally unresolved. We developed a two-step computational...

Thrilled to share that the final piece of my PhD work is now on bioRxiv! biorxiv.org/content/10.1... With support from @nvidia and the @NSF, we used AlphaFold to screen 1.6M+ protein pairs, revealing thousands of potential novel PPIs. All data can be viewed at predictomes.org/hp

The composition and structure of the outer kinetochore KMN complex is conserved across kingdoms - Communications Biology Affinity purification in Arabidopsis identified all key subunits of the outer kinetochore KMN complex. Functional analyses revealed a striking conservation of its composition and organization across k...

www.nature.com/articles/s42...

Latest from the lab. The conclusion is in the title!
Basically, we found that the KMN complex (outer kinetochore) is fully conserved between plants and fungi/animals, showing deep origin. (reminder, you are closer to a mushroom than a mushroom is to a plant.)

Among the anti-recombinases, FIGNL1 rules them all. So much that inactivating it brings BRCA2-deficient cells to life. Who is responsible for RAD51 loading without BRCA2/FIGNL1, check out the paper to find out! Great collaboration with @raychaudhurilab.bsky.social

www.science.org/doi/10.1126/...

Excited to release BoltzGen which brings SOTA folding performance to binder design! The best part of this project is collaborating with a broad network of leading wetlabs that test BoltzGen at an unprecedented scale, showing success on many novel targets and pushing the model to its limits!

High-throughput evaluation of genetic variants with prime editing sensor libraries - Nature Biotechnology Prime editing sensor libraries evaluate diverse genetic variants in their endogenous genomic contexts.

Prime editing sensor libraries evaluate diverse genetic variants in their endogenous genomic contexts go.nature.com/49Q1WCQ
rdcu.be/eLVts

Super excited about first Shendure/Baker Lab collaboration & preprint on a multiplex sequencing-based strategy for screening de novo proteome editors in mammalian cells. Kudos to the brilliant Chase Suiter (not here) & @greenahn.bsky.social on the work! Preprint here:
www.biorxiv.org/content/10.1...

Thrilled to announce our new preprint, “Protein Hunter: Exploiting Structure Hallucination within Diffusion for Protein Design,” in collaboration with @Griffin, @GBhardwaj8 and @sokrypton.org

🧬Code and notebooks will be released by the end of this week.
🎧Golden- Kpop Demon Hunters

GPU-accelerated homology search with MMseqs2 - Nature Methods Graphics processing unit-accelerated MMseqs2 offers tremendous speedups for homology retrieval from metagenomic databases, query-centered multiple sequence alignment generation for structure predictio...

GPU-accelerated MMseqs2 offers tremendous speedup for homology retrieval, protein structure prediction with ColabFold, and protein structure search with Foldseek. @martinsteinegger.bsky.social @milot.bsky.social @machine.learning.bio

www.nature.com/articles/s41...

Exciting to see our protein binder design pipeline BindCraft published in its final form in @Nature ! This has been an amazing collaborative effort with Lennart, Christian, @sokrypton.org, Bruno and many other amazing lab members and collaborators.

www.nature.com/articles/s41...

📌

AI-generated MLH1 small binder improves prime editing efficiency A compact, AI-generated suppressor of DNA mismatch repair can enhance prime editing in vivo and in vitro and can be integrated into a variety of prime editing architectures.

Now online! AI-generated MLH1 small binder improves prime editing efficiency

RPA directly stimulates Mer3/HFM1 helicase processivity to ensure normal crossover formation in meiosis Meiotic crossover formation is critical for generating viable gametes and enhancing genetic diversity. The helicase Mer3 (HFM1 in humans) is a highly conserved factor essential for promoting crossover...

www.biorxiv.org/content/10.1...

Folddisco finds similar (dis)continuous 3D motifs in large protein structure databases. Its efficient index enables fast uncharacterized active site annotation, protein conformational state analysis and PPI interface comparison. 1/9🧶🧬
📄 www.biorxiv.org/content/10.1...
🌐 search.foldseek.com/folddisco

AI just cracked de novo antibody design with a 100x leap! 🧪

Chai-2, a next-gen multimodal generative model, is shaking up protein design. With a 16% hit rate in fully de novo antibody design—over 100 times better than previous methods—it’s making drug discovery faster and more precise than ever.

Excited to unveil Boltz-2, our new model capable not only of predicting structures but also binding affinities! Boltz-2 is the first AI model to approach the performance of FEP simulations while being more than 1000x faster! All open-sourced under MIT license! A thread… 🤗🚀

🚀 Excited to release BoltzDesign1!

✨ Now with LogMD-based trajectory visualization.
🔗 Demo: rcsb.ai/ff9c2b1ee8
Feedback & collabs welcome! 🙌

🔗: GitHub: github.com/yehlincho/Bo...
🔗: Colab: colab.research.google.com/github/yehli...
@sokrypton.org @martinpacesa.bsky.social

@science.org 🧫🧬❄️🔬 Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis | Science www.science.org/doi/10.1126/...
@yiweichang.bsky.social www.yiweichanglab.org @jiwasa.bsky.social #virology #Influenza #Cryo-EM #StructuralBiology #RNA #polymerase

Solid phase transitions as a solution to the genome folding paradox - Nature In vitro reconstitution and in vivo live-cell imaging of LHX2–EBF1–LDB1 enhancer hubs in olfactory sensory neurons reveals that these transcription factors form condensates with solid, rathe...

Forget liquid-liquid phase separation, here comes solid phase transition 😱

www.nature.com/articles/s41...

A tripartite protein complex promotes DNA transport during natural transformation in firmicutes. Natural genetic transformation is a conserved mechanism of bacterial horizontal gene transfer, which is directed entirely by the recipient cell and facilitates the acquisition of new genetic traits su...

Pleased to share a new preprint - a great collaboration with @jessicaandreani.bsky.social and the Guerois lab at I2BC, and the Radicella lab at the CEA. Using stuctural modelling, we reveal & validate a 3 protein complex involved in DNA import during transformation.

www.biorxiv.org/content/10.1...

Please see our latest paper on the role of EXO1 in meiosis: "EXO1 promotes the meiotic MLH1-MLH3 endonuclease through conserved interactions with MLH1, MSH4 and DNA". Congratulations to both first authors, Megha Roy and Aurore Sanchez and thanks to all our collaborators!

Happy to share our DNA Repair special issue on the replication stress response curated with @vindignilab.bsky.social.
www.sciencedirect.com/special-issu...