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bioRxiv · 10.1101/2025.07.06.663357

Structural motif search across the protein-universe with Folddisco

Kim, H.·Kim, R. S.·Mirdita, M.·Steinegger, M.
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Abstract

Detecting similar protein structural motifs, functionally crucial short 3D patterns, in large structure collections is computationally prohibitive. Therefore, we developed Folddisco, which overcomes this through an index of position-independent geometric features, including side-chain orientation, combined with a rarity-based scoring system. Folddiscos compact 1.45-terabyte index of 53 million AFDB50 structures enables querying this database within seconds. It is 20-fold faster in querying and 4-fold more storage-efficient than existing methods. Folddisco is more accurate and storage-efficient than state-of-the-art methods, while being an order of magnitude faster. Folddisco is free software available at folddisco.foldseek.com and a webserver at search.foldseek.com/folddisco.

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Kim, H., Kim, R. S., Mirdita, M., Steinegger, M.. 2025-07-06. Structural motif search across the protein-universe with Folddisco. https://doi.org/10.1101/2025.07.06.663357

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