Such an incredible journey building DISCO 🪩. Love working with this team. DISCO is a co-design model with functional, de novo, new-to-nature enzymes. Huge shoutout to my co-authors for making this a reality! 🚀👇
How much information does it take to fold a protein? Not much, if you use the right information! We find that residue burial, a binary label of core vs surface, encodes a protein's fold highly efficiently and even improves ESM2's structure representation. 1/8 www.biorxiv.org/content/10.6...
Added a JAX translation of the excellent Proteina-Complexa (from nvidia, @kdidi.bsky.social , @karstenkreis.bsky.social ) to mosaic. You can do beam search with any mosaic loss (e.g. protenix + mpnn) and JAX with generate efficient GPU/TPU code.
Meet evedesign: open-source AI, accessible protein design
✅Combine models for multiobjective optimization
✅Integrate experimental data
✅ Run on your own infrastructure
📄Paper: www.biorxiv.org/content/10.6...
💻Code: github.com/evedesignbio
🌐Webserver: evedesign.bio
Collaborate: hello@evedesign.bio
I think the boltzdesign1 method does something similar when using the confidence module (for plddt,pae,ptm) in the optimisation loop.
📢📢 Proteina-Complexa 📢📢
Atomistic Binder Design with Generative Pretraining and Test-Time Compute + Experimental Validation at Scale
⭐️ Project page (research.nvidia.com/labs/genair/...) for:
📜 Method paper (ICLR' 2026 Oral)
🧬 Wet lab paper
🛠️ Code & Models
📁 Data
🧵 Thread
(1/n)
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
New preprint🚨
Imagine (re)designing a protein via inverse folding. AF2 predicts the designed sequence to a structure with pLDDT 94 & you get 1.8 Å RMSD to the input. Perfect design?
What if I told u that the structure has 4 solvent-exposed Trp and 3 Pro where a Gly should be?
Why to be wary🧵👇
I thoroughly recommend reading all of Cory Doctorow's recent speech on AI skepticism, it's crammed with new arguments and interesting new ways of thinking about these problems pluralistic.net/2025/12/05/pop-that-bubb...
Introducing gRNAde: our own little "AlphaGo Moment" for RNA design! 🧬🚀
📝: tinyurl.com/gRNAde-paper
Unlike proteins, RNA design has long relied on "wisdom of the crowd" (human experts) or the slow crawl of directed evolution — gRNAde changes that! 🧵👇
Guiding Generative Models for Protein Design: Prompting, Steering and Aligning
Figure 1
Figure 2
Table 1
Guiding Generative Models for Protein Design: Prompting, Steering and Aligning [new]
Reviews methods to guide generative models to design proteins with specific properties, even if rare in training data. Focuses on parameter and fixed-model methods.
Global Analysis of Aggregation Determinants in Small Protein Domains www.biorxiv.org/content/10.1101/2025.11....
Re recent AFDB update, in case you wondered:
- most of AFDB is still same original predictions
-new/changed entries were modeled with AF2
- the MSAs are the originals, so should not contain sequences from last few years
De novo design of All-atom biomolecular interactions with RFdiffusion3 www.biorxiv.org/content/10.1...
Protein functional site annotation using local structure embeddings | PNAS www.pnas.org/doi/10.1073/...
RFdiffusion2 is now live!
github.com/RosettaCommo...
You can now design proteins, and in particular enzymes from just partially defined amino acid side chains, and without defining their sequence position or order!
Scaling down protein language modeling with MSA Pairformer
Figure 1
Figure 2
Figure 3
Scaling down protein language modeling with MSA Pairformer [new]
...Pairformer: memory-efficient MSA, bi-directional updates, better evol. signals, outperforms larger models.
There is @aixbiobot.bsky.social who does a similar thing.
PS, I found Vidu to work better for interprolation between images. Example attached:
Structural motif search across the protein-universe with Folddisco www.biorxiv.org/content/10.1101/2025.07....
Hello all Protein Cosmos 🧶🧬 followers. A new Protein Cosmos feed had been set up with a new host. You will need to search Protein Cosmos and add the new feed to your account. Apologies and thanks to @blueskyfeeds.com for all their support to get us started. Best luck for the future!
New preprint 🚨--protein language models + MD training ➡️ allosteric networks!
@sonyahanson.bsky.social and I are developing RocketSHP 🚀 for rapid genome-scale inference of local+correlated fluctuations + structure token distributions!
📄: www.biorxiv.org/content/10.1...
💻: github.com/flatironinst...
For a similar pipeline, there is also juv github.com/manzt/juv that extends uv to jupyter notebooks including inline script metadata (PEP 723).
A case study on the challenges of evaluating AI predictions in biology and the implications for published results.
1/2
rachel.fast.ai/posts/2025-0...
The war on science in the US is already having an effect on private sector research like AlphaFold. Bears repeating but the private sector builds on top of things created by academic research for the public good. This hurts everyone.
To the world:
We are fighting back. Our movement has been silenced by the media here—but we are not backing down. This is what our streets looked like across multiple cities. Tomorrow, there will be more of us! Raise a glass to freedom.
—With love,
Your American allies.
Sharing slides for All-atom Diffusion Transformers
- briefly summarises the big ideas and key takeaways
Link - www.chaitjo.com/publication/...
From a colleague in my PhD lab! Chase presents her method OMEGA, a simple, scalable method to assemble 100s-1000s of custom genes from oligo pools using standard lab tools!
#synbio #proteinengineering #OMEGA
