Structural motif search across the protein universe with Folddisco.

Kim, Hyunbin; Kim, Rachel Seongeun; Mirdita, Milot; Yoon, Jaewon; Steinegger, Martin · Nat Biotechnol · 2026

basic_science · Level V

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Abstract

Detecting similar protein structural motifs in large structure collections is computationally expensive. We developed Folddisco, a fast structural motif search tool that uses an index of position-independent geometric features, including side-chain orientation, combined with a rarity-based scoring system. Folddisco is 20-fold faster in querying and fourfold more storage-efficient than existing methods while improving accuracy. Folddisco is freely available online ( https://folddisco.foldseek.com ), along with a webserver ( https://search.foldseek.com/folddisco ).