DALI 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 () 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 the previously characterized families, generating a functional hypothesis that can be explored downstream in structural biology studies. Other findings include gene fusions, tandem duplications, and adjustments to domain boundaries. The evidence for homology can be browsed interactively through live examples on DALI's website.

Automated summary

Structural comparison can detect remote homology missed by sequence comparison. The DALI web server offers structural analysis tools such as database searches, interactive visualization, and 3D structure alignment. In this study, we used DALI to mine the AlphaFold Database and discovered 100 previously unreported remote homologous relationships. The findings provided insights into protein families and allowed for the generation of functional hypotheses for further exploration in structural biology studies.