Structural motif search across the protein-universe with Folddisco

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. Folddisco’s compact 1.45-terabyte index of 53 million AFDB50 structures enables querying this database within seconds. It is up to 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 https://folddisco.foldseek.com and a webserver at https://search.foldseek.com/folddisco.