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AlphaFill: enriching the AlphaFold models with ligands and co-factors
Open accessPreprint — published as 10.1038/s41592-022-01685-y · Paper page
Abstract
Artificial intelligence (AI) methods for constructing structural models of proteins on the basis of their sequence are having a transformative effect in biomolecular sciences. The AlphaFold protein structure database makes available hundreds of thousands of protein structures. However, all these structures lack cofactors essential for their structural integrity and molecular function (e.g. hemoglobin lacks a bound heme), key ions essential for structural integrity (e.g. zinc-finger motifs) or catalysis (e.g. Ca 2+ or Zn 2+ in metalloproteases), and ligands that are important for biological function (e.g. kinase structures lack ADP or ATP). Here, we present AlphaFill, an algorithm based on sequence and structure similarity, to “transplant” such “missing” small molecules and ions from experimentally determined structures to predicted protein models. These publicly available structural annotations are mapped to predicted protein models, to help scientists interpret biological function and design experiments.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Flagged first, then by citations
Research works printed but not linked: 45
- 10.1126/science.abj8754 · DOI · Paper page
- 2021, Highly accurate protein structure prediction for the human proteome, Nature, 596, 590, 10.1038/s41586-021-03828-1 · DOI · Paper page
- 2021, AI revolutions in biology, EMBO reports, 22, e54046, 10.15252/embr.202154046 · DOI · Paper page
- 10.1101/2021.10.04.463034 · DOI · Paper page
- 10.1126/science.abm4805 · DOI · Paper page
- 10.1002/pro.3353 · DOI
- 10.1006/jmbi.1990.9999 · DOI · Paper page
- 2021, LAHMA: structure analysis through local annotation of homology-matched amino acids, Acta Cryst D, 77, 28, 10.1107/S2059798320014473 · DOI
- 2018, Homology-based loop modeling yields more complete crystallographic protein structures, IUCrJ, 5, 585, 10.1107/S2052252518010552 · DOI
- 2020, The quaternion-based spatial-coordinate and orientation-frame alignment problems, Acta Cryst A, 76, 432, 10.1107/S2053273320002648 · DOI
- 10.1093/bioinformatics/btq442 · DOI
- 2021, Mol* Viewer: modern web app for 3D visualization and analysis of large biomolecular structures, Nucleic Acids Research, 49, W431, 10.1093/nar/gkab314 · DOI · Paper page
- 10.1021/ja067546r · DOI
- 10.1021/ja404900k · DOI
- 10.1093/nar/gkaa1100 · DOI · Paper page
- PDBe-KB consortium, 2020, PDBe-KB: a community-driven resource for structural and functional annotations, Nucleic Acids Research, 48, D344, 10.1093/nar/gkz853 · DOI
- 10.1038/35002641 · DOI
- 2021, Rational design of metal-binding sites in domain-swapped myoglobin dimers, Journal of Inorganic Biochemistry, 217, 111374, 10.1016/j.jinorgbio.2021.111374 · DOI
- 10.1002/pro.5560070805 · DOI · Paper page
- 2008, Evolution of binding sites for zinc and calcium ions playing structural roles, Proteins: Structure, Function, and Bioinformatics, 71, 813, 10.1002/prot.21741 · DOI
- 2016, Validation and correction of Zn–CysxHisy complexes, Acta Cryst D, 72, 1110, 10.1107/S2059798316013036 · DOI
- 10.1016/j.jmb.2011.08.029 · DOI
- 10.1073/pnas.251664698 · DOI
- 10.1038/emboj.2011.243 · DOI
- 10.1016/j.tibs.2005.08.005 · DOI
- 2020, Crystal structures of human ENPP1 in apo and bound forms, Acta Cryst D, 76, 889, 10.1107/S2059798320010505 · DOI
- 10.1021/acs.jmedchem.7b00032 · DOI
- 2018, Structural basis for nucleotide recognition by the ectoenzyme CD203c, The FEBS Journal, 285, 2481, 10.1111/febs.14489 · DOI
- 10.1074/jbc.M113.505867 · DOI
- 2017, A key tyrosine substitution restricts nucleotide hydrolysis by the ectoenzyme NPP5, The FEBS Journal, 284, 3718, 10.1111/febs.14266 · DOI
- 2016, Structure and biological function of ENPP6, a choline-specific glycerophosphodiester-phosphodiesterase, Sci Rep, 6, 20995, 10.1038/srep20995 · DOI
- 10.1074/jbc.M116.769273 · DOI
- 10.1016/j.molcel.2007.04.018 · DOI
- 10.1038/35037523 · DOI
- 10.1073/pnas.1814279116 · DOI · Paper page
- 10.1371/journal.pbio.0040144 · DOI
- 2021, The case for post-predictional modifications in the AlphaFold Protein Structure Database, Nat Struct Mol Biol, 28, 869, 10.1038/s41594-021-00680-9 · DOI
- 10.1007/978-1-0716-0270-6_3 · DOI
- 10.1107/S0907444904026460 · DOI
- 10.1093/bioinformatics/bth214 · DOI
- 10.1093/nar/gki422 · DOI
- 2003, IUCr Computing Commission Newsletter, The Clipper C++ libraries for X-ray crystallography, 2, 4
- 10.1093/nar/gkq1105 · DOI
- 10.1107/S0907444910007493 · DOI · Paper page
- 10.1107/S0907444911007281 · DOI
Metadata
- Authors
- Hekkelman, M. L., de Vries, I., Joosten, R. P., & Perrakis, A.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Corresponding author
- Joosten, Robbie P.
- Venue
- Nature Methods
- Publisher
- openRxiv
- Published
- 2021-11-27
- Volume
- 20
- Issue
- 2
- Pages
- 205-213
- ISSN
- 1548-7091 (ISSN-L)
- PMC
- PMC9911346
- OpenAlex
- W4310058955
- Cited by
- 511
- References
- 1
- Citations by year
- 2026: 99 · 2025: 117 · 2024: 160 · 2023: 107 · 2022: 28
- FWCI
- 33.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Nature Methods (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- European Commission (HORIZON2020, 871037)
- Ministerie van Volksgezondheid, Welzijn en Sport
- KWF Kankerbestrijding
- Horizon 2020 Framework Programme (871037)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
- Keywords
- AlphaFold, protein structure prediction, cofactors, metal ions, small molecule binding, structural similarity, sequence similarity, protein-ligand binding, protein structure database
- MeSH terms
- Artificial Intelligence, Ions, Ligands, Protein Conformation, Proteins, Zinc
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