Folddisco is now published @natbiotech.nature.com. It’s a fast motif search for similar 3D DISCOntinuous residues like catalytic sites or zinc fingers across the entire protein universe.
📄 www.nature.com/articles/s41...
💾 folddisco.foldseek.com
🌐 https://search.foldseek.com/folddisco
Meet the Folddisco Marv, designed by Hyunbin Kim, who also developed Folddisco.
A case from M-CSA: these two enzymes share a fold (high TM-score, low RMSD) but have different active sites and different EC numbers (3.8.1.6 vs 4.2.1.17). Annotation by fold alone would group them together. Folddisco reads the active site instead.
🧵5/7
Webserver now pairs with Foldseek & FoldMason: search, motif detection & structure alignment in one workflow. Free, open source, prebuilt indices for AFDB50, PDB, ESM30, BFVD & more. With @milot.bsky.social, @eunbelivable.bsky.social & Cameron L. M. Gilchrist search.foldseek.com/folddisco
🧵6/7
Folddisco enables protein structural motif search in million scale databases.
Structural motif search across the protein universe with Folddisco - @martinsteinegger.bsky.social go.nature.com/4g8lCb0
So grateful to my collaborators @eunbelivable.bsky.social , @milot.bsky.social, @jwyoon05.bsky.social, and my advisor @martinsteinegger.bsky.social, plus the whole SteineggerLab 🙏
🔗 steineggerlab.com
👥 bsky.app/starter-pack...
🧵7/7
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
Martin Steinegger 🇺🇦
Video
Nature Biotechnology
New in the published version: a verified allosteric motif search. Querying active + allosteric sites together, Folddisco recovers both in 82.9% of cases, pinpointing functional sites that cooperate across a protein. (led by @eunbelivable.bsky.social)
🧵3/7
Does your designed active site already exist in nature? Is an uncharacterized protein hiding a catalytic site or a pocket? Folddisco answers both, searching millions of structures for a 3D motif in seconds.
@natbiotech.nature.com 🧬
📄 www.nature.com/articles/s41...
🧵1/7👇
How? We index every residue pair within 20Å as position-independent geometric features (incl. side-chain orientation). One index serves any motif: short catalytic sites or long discontinuous segments.
20x faster querying and a 4x smaller index than prior tools, with better accuracy.
🧵2/7
Martin Steinegger 🇺🇦
Folddisco enables protein structural motif search in million scale databases.
We also added an M-CSA benchmark to probe enzyme active-site search. On hand-curated catalytic sites, Folddisco improves sensitivity by 25.6% over pyScoMotif (AUC 0.432 vs 0.344), up to 0.463 in sensitive mode. Better at finding the residues that do the chemistry. 🧪
🧵4/7
go.nature.com
Folddisco enables protein structural motif search in million scale databases.
