Exploring structural diversity across the protein universe with The Encyclopedia of Domains

• 成果类型: Article
• 署名作者: Lau, Andy M.; Bordin, Nicola; Kandathil, Shaun M.; Sillitoe, Ian; Waman, Vaishali P.; Wells, Jude; Orengo, Christine A.; Jones, David T.
• 署名单位: University of London; University College London; University of London; University College London; Birkbeck University London; University of London; University College London
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8319
• DOI: 10.1126/science.adq4946
• 发表日期: 2024-11-01
• 关键词: Classification; scop; cath; sequence; database; SPACE

摘要

The AlphaFold Protein Structure Database (AFDB) contains more than 214 million predicted protein structures composed of domains, which are independently folding units found in multiple structural and functional contexts. Identifying domains can enable many functional and evolutionary analyses but has remained challenging because of the sheer scale of the data. Using deep learning methods, we have detected and classified every domain in the AFDB, producing The Encyclopedia of Domains. We detected nearly 365 million domains, over 100 million more than can be found by sequence methods, covering more than 1 million taxa. Reassuringly, 77% of the nonredundant domains are similar to known superfamilies, greatly expanding representation of their domain space. We uncovered more than 10,000 new structural interactions between superfamilies and thousands of new folds across the fold space continuum.