biostudies-literatureHolm LNovo Nordisk Fondene4519https://www.ebi.ac.uk/biostudies/studies/S-EPMC9793968biostudies-literatureUnknown32(1)Structural comparison reveals remote homology that often fails to be detected by sequence comparison. The DALI web server (http://ekhidna2.biocenter.helsinki.fi/dali) is a platform for structural analysis that provides database searches and interactive visualization, including structural alignments annotated with secondary structure, protein families and sequence logos, and 3D structure superimposition supported by color-coded sequence and structure conservation. Here, we are using DALI to mine the AlphaFold Database version 1, which increased the structural coverage of protein families by 20%. We found 100 remote homologous relationships hitherto unreported in the current reference database for protein domains, Pfam 35.0. In particular, we linked 35 domains of unknown function (DUFs) to tProtein science : a publication of the Protein SocietyDALI shines a light on remote homologs: One hundred discoveries.PMC9793968NNF200C0065157Laiho AToronen PSalgado MHolm LfalseDALI shines a light on remote homologs: One hundred discoveries.Structural comparison reveals remote homology that often fails to be detected by sequence comparison. The DALI web server (http://ekhidna2.biocenter.helsinki.fi/dali) is a platform for structural analysis that provides database searches and interactive visualization, including structural alignments annotated with secondary structure, protein families and sequence logos, and 3D structure superimposition supported by color-coded sequence and structure conservation. Here, we are using DALI to mine the AlphaFold Database version 1, which increased the structural coverage of protein families by 20%. We found 100 remote homologous relationships hitherto unreported in the current reference database for protein domains, Pfam 35.0. In particular, we linked 35 domains of unknown function (DUFs) to t2023-01-01T00:00:00Z2023 Jan2026-07-14T22:40:17.937Z2025-02-19T01:44:29.659ZS-EPMC97939683641924810.1002/pro.4519