You asked, we listened. Millions of AI-predicted protein complex structures are now available in the #AlphaFold Database.
This spans homodimers from 20 of the most studied species, including humans, as well as the World Health Organization’s priority pathogens list.
www.ebi.ac.uk/about/news/t...
The Critical Assessment of Structure Prediction (CASP) experiment is calling for prediction targets: Immune Complexes, Organic Ligand-Protein Complexes, Nucleic Acids and Complexes, Conformational Ensembles, Difficult Protein Structures and Complexes. Rule of Thumb: If AlphaFold3 can generate a high-quality model, it is likely not a CASP-grade challenge. If it struggles, we want it.
Is #AI hitting a plateau in structure prediction? Help us find out at CASP17! 🧪🧬
Calling for Targets: Immune Complexes, protein - ligand complexes, RNA/DNA, conformational ensembles, membrane proteins, viral origins, and large complexes.
The Rule of Thumb: If AF3 can’t model it, we want it.
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
Isomorphic Labs Drug Design Engine (IsoDDE), a unified computational drug-design system
Announcement:
www.isomorphiclabs.com/articles/the...
Report:
storage.googleapis.com/isomorphicla...
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...
Here are the success rates of de novo pipelines based on which designs I could actually identify the methods for.
Loved this post from A-Alpha: aalphabio.substack.com/p/building-a.... If anything I think the IPSAE (or any other post-hoc metric) picture is even worse than they show: after optimization the fraction of false positives would (probably) be even higher than in this dataset
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'm really excited to break up the holiday relaxation time with a new preprint that benchmarks AlphaFold3 (AF3)/“co-folding” methods with 2 new stringent performance tests.
Thread below - but first some links:
A longer take:
fraserlab.com/2025/12/29/k...
Preprint:
www.biorxiv.org/content/10.6...
Figure comparing runtime and VRAM utilization between Boltz-2 (baseline), and LMI4Boltz (+memory, and +chunk). Main plot: runtime (y-axis) versus token count (x-axis), showing that all methods scale similarly, with +memory and +chunk handling larger token counts. Inset scatterplot: PDB test lDDT scores from Boltz-2 versus LMI4Boltz, showing a strong linear correlation (values near y = x). Right panels: – Top bar chart: maximum tokens processable on a 24 GB GPU increase from 1596 (Boltz-2) to 2356 (+memory) and 2660 (+chunk). – Bottom bar chart: H200 runtime for 1596 tokens remains comparable across methods.
🧶🧬 We present LMi4Boltz:
www.biorxiv.org/content/10.1...
Boltz-2 is an excellent open source alternative to AlphaFold3. However, high VRAM use restricts modeling large complexes. Using careful memory management, we increase the Boltz-2 size limit by >60% while maintaining execution speed.
I don't believe that is the consensus. Novel folds can be well predicted if there is strong support from evolutionary information.
I guess any holo structure template implicitly biases the model towards a known ligand-binding site. It would be interesting to know the ceiling of what can be achieved with this implicit information by providing the native ligand holo structure (kind of cross-docking vs re-docking).
When using the ground-truth template AF3 did not achieve perfect fidelity or the template issue only affected a subset of systems?
