In Nature ; h5-index 368.0
Protein structures can provide invaluable information, both for reasoning about biological processes and for enabling interventions such as structure-based drug development or targeted mutagenesis. After decades of effort, 17% of the total residues in human protein sequences are covered by an experimentally-determined structure1. Here we dramatically expand structural coverage by applying the state-of-the-art machine learning method, AlphaFold2, at scale to almost the entire human proteome (98.5% of human proteins). The resulting dataset covers 58% of residues with a confident prediction, of which a subset (36% of all residues) have very high confidence. We introduce several metrics developed by building on the AlphaFold model, and use them to interpret the dataset, identifying strong multi-domain predictions as well as regions likely to be disordered. Finally, we provide some case studies illustrating how high-quality predictions may be used to generate biological hypotheses. Importantly, we are making our predictions freely available to the community via a public database (hosted by the European Bioinformatics Institute at https://alphafold.ebi.ac.uk/ ). We anticipate that routine large-scale and high-accuracy structure prediction will become an important tool, allowing new questions to be addressed from a structural perspective.
Tunyasuvunakool Kathryn, Adler Jonas, Wu Zachary, Green Tim, Zielinski Michal, Žídek Augustin, Bridgland Alex, Cowie Andrew, Meyer Clemens, Laydon Agata, Velankar Sameer, Kleywegt Gerard J, Bateman Alex, Evans Richard, Pritzel Alexander, Figurnov Michael, Ronneberger Olaf, Bates Russ, Kohl Simon A A, Potapenko Anna, Ballard Andrew J, Romera-Paredes Bernardino, Nikolov Stanislav, Jain Rishub, Clancy Ellen, Reiman David, Petersen Stig, Senior Andrew W, Kavukcuoglu Koray, Birney Ewan, Kohli Pushmeet, Jumper John, Hassabis Demis