Protein Structure Informed Bacteriophage Genome Annotation with Phold https://www.biorxiv.org/content/10.1101/2025.08.05.668817v1

Folddisco webserver result view update: - Added description texts for AFDB - Integrated TaxoView taxonomy visualization & filter by @sunjaelee.bsky.social - Inter-residue distance clustering by DBSCAN to explore motif diversity. 🌐 search.foldseek.com/folddisco 📄 www.biorxiv.org/content/10.1...

Today at 2 PM at 3DSIG #ISMBECCB2025, @nbordin.bsky.social presents our joint work on metagenomic-scale clustering and novel domain discovery in predicted structures! 📄 www.biorxiv.org/content/10.1... Also check out poster: B-50 lolalign Sensitive structural alignments by Lasse B-123 BFVD by Rachel

Our new preprint is out! www.biorxiv.org/content/10.1... In this study, we present the largest systematic analysis of microbiome structure and function, integrating 85K uniformly processed metagenomes from diverse habitats worldwide. @podlesny.bsky.social @jonas-bio.bsky.social @borklab.bsky.social

Today at 5pm, @eunbelivable.bsky.social will present her work on the Big Fantastic Viral Database (BFVD) at #ISMB2025 in BOSC. She also has a poster B-123 (tomorrow, 22nd), so please drop by to have ta chat and grab some stickers! 📄 academic.oup.com/nar/article/...

I’m excited to share our #Folddisco preprint! 🚀 We introduce a novel pairwise-geometric feature set and an optimized index structure to enable scalable structural motif search. Dive into our case studies and key results here: www.biorxiv.org/content/10.1...

Folddisco accurately detects discontinuous motifs like zinc fingers and segment-based motifs, previously requiring separate tools. Additionally, we built a SCOPe benchmark by sampling conserved residues from families and measuring the recall up to the first false positive. 3/9

Folddisco builds indexes faster and smaller than previous tools: indexing AFDB50 (53M structures) takes only ~24h vs. ~20 days (extrapolated) for pyScoMotif. Querying a zinc-finger motif across AFDB50 takes just ~13s, up to 48x faster than pyScoMotif. 4/9

Folddisco can annotate proteins: querying a canonical zinc-finger uncovers an uncharacterized oyster protein and metagenomic proteins. It also detects partial catalytic metal sites in E. coli peptide deformylase. All of these hits would be missed by Foldseek or sequence aligners. 5/9

Folddisco can distinguish functional states. We searched GPCR activation motifs (CWxP, NPxxY, DRY), clearly separating active/inactive states. A search in the AFDB shows ~53% active, closely mirroring experimental PDB 54%, suggesting AlphaFold might follow its training conformation distribution. 6/9

Folddisco can be applied for PPI interface searches. When querying an interface between antibody chains (gray/black), it successfully identifies matching interfaces within monomeric antibody fragments (cyan), showcasing its potential to detect novel interaction partners and interfaces. 7/9

We provide a user-friendly Folddisco webserver, enabling instant structural motif searches in PDB, AFDB-Proteomes, AFDB50 (available later today), and ESMatlas (ESM30). Explore it here: search.foldseek.com/folddisco 8/9

Structural motif search across the protein-universe with Folddisco https://www.biorxiv.org/content/10.1101/2025.07.06.663357v1

We've updated our AFESM website to now include biome filtering, allowing exploration of protein structures adapted to specific environments. 🌐 afesm.foldseek.com Read more about the work in the skeetorial 🦋 bsky.app/profile/mart... or our preprint 📄 www.biorxiv.org/content/10.1...

We identified 11,941 novel multi-domain combinations. We found membrane-associated domains (e.g., TonB dependent receptor, highlighting domain recombination rather than new folds as a driver of structural innovation. 5/n

ESMatlas uses MGnify environmental labels. Leveraging this, we computed the lowest common biomes per structural cluster, revealing protein adaptations unique to specific environments, especially extreme ones like hyperthermal, hypersaline, and glaciers. 3/n

AFESM: a metagenomic guide through the protein structure universe! We clustered 821M structures (AFDB&ESMatlas) into 5.12M groups; revealing biome-specific groups, only 1 new fold even after AlphaFold2 re-prediction & many novel domain combos. 🧵 🌐 afesm.foldseek.com 📄 www.biorxiv.org/content/10.1...

It's a big collaborative effort by @jingiyeo.bsky.social @yewonhan.bsky.social @nbordin.bsky.social, Andy Lau, Shaun M. Kandathil, @hbkgenomics.bsky.social, Eli Levy Karin, @milot.bsky.social David T. Jones and Christine Orengo. Visit our #RECOMB2025 poster (719) & talk (1 pm at B145 on April 29).

Check out Folddisco poster at #RECOMB2025!

SNU Profs Woon Ju Song & Martin Steinegger (Biology) developed the AI-based SeekRank algorithm to discover enzymes for cancer immunotherapy. doi.org/10.1093/nar/...