Implications of AlphaFold 2 for crystallographic phasing by molecular replacement
Open accessPublished version of a preprint
Abstract
The AlphaFold2 results in the 14th edition of Critical Assessment of Structure Prediction (CASP14) showed that accurate (low root-mean-square deviation) in silico models of protein structure domains are on the horizon, whether or not the protein is related to known structures through high-coverage sequence similarity. As highly accurate models become available, generated by harnessing the power of correlated mutations and deep learning, one of the aspects of structural biology to be impacted will be methods of phasing in crystallography. Here, the data from CASP14 are used to explore the prospects for changes in phasing methods, and in particular to explore the prospects for molecular-replacement phasing using in silico models.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
AF2 models are increasingly used in X-ray crystallographic molecular replacement and phasing.
“AF2 models have also been increasingly used during molecular replacement and phasing of X-ray diffraction data obtained from protein crystals76–79”
From The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins (2024) · cites this paper as [78]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Sheldrick, G. M. (2007) · Acta Crystallographica Section A Foundations of Crystallography · doi:10.1107/s0108767307043930 · Cited by 87,861 · see citing works
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 · see citing works
<i>Phaser</i> crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612 · see citing works
Self-citationRefinement of Macromolecular Structures by the Maximum-Likelihood Method
Murshudov, G. N., Vagin, A. A., & Dodson, E. J. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444996012255 · Cited by 14,671 · see citing works
Overview of the <i>CCP</i> 4 suite and current developments
Winn, M. D., Ballard, C. C., Cowtan, K. D., Dodson, E. J., Emsley, P., Evans, P. R., Keegan, R. M., Krissinel, E. B., Leslie, A. G. W., McCoy, A., et al. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910045749 · Cited by 12,353 · see citing works
Self-citationREFMAC 5 for the refinement of macromolecular crystal structures
Murshudov, G. N., Skubák, P., Lebedev, A. A., Pannu, N. S., Steiner, R. A., Nicholls, R. A., Winn, M., Long, F., & Vagin, A. A. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444911001314 · Cited by 8,385 · see citing works
Highly accurate protein structure prediction for the human proteome
Tunyasuvunakool, K., Adler, J., Wu, Z., Green, T., Zielinski, M., Žídek, A., Bridgland, A., Cowie, A., Meyer, C., Laydon, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03828-1 · Cited by 3,025 · see citing works
Perineuronal nets stabilize the grid cell network
Christensen, A. C., Lensjø, K. K., Lepperød, M. E., Dragly, S.-A., Sutterud, H., Blackstad, J. S., Fyhn, M., & Hafting, T. (2021) · Nature Communications · doi:10.1038/s41467-020-20241-w · Cited by 1,865 · see citing works
Mol* Viewer: modern web app for 3D visualization and analysis of large biomolecular structures
Sehnal, D., Bittrich, S., Deshpande, M., Svobodová, R., Berka, K., Bazgier, V., Velankar, S., Burley, S. K., Koča, J., & Rose, A. S. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab314 · Cited by 1,154 · see citing works
LGA: a method for finding 3D similarities in protein structures
Zemla, A. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg571 · Cited by 1,069 · see citing works
‘It will change everything’: DeepMind’s AI makes gigantic leap in solving protein structures
Callaway, E. (2020) · Nature · doi:10.1038/d41586-020-03348-4 · Cited by 499 · see citing works
High-resolution structure prediction and the crystallographic phase problem
Qian, B., Raman, S., Das, R., Bradley, P. H., McCoy, A. J., Read, R. J., & Baker, D. A. (2007) · Nature · doi:10.1038/nature06249 · Cited by 317 · see citing works
Self-citationHigh‐accuracy protein structure prediction in <scp>CASP14</scp>
Pereira, J., Simpkin, A. J., Hartmann, M. D., Rigden, D. J., Keegan, R. M., & Lupas, A. N. (2021) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.26171 · Cited by 314 · see citing works
Improved protein structure refinement guided by deep learning based accuracy estimation
Hiranuma, N., Park, H., Baek, M., Anishchenko, I., Dauparas, J., & Baker, D. (2021) · Nature Communications · doi:10.1038/s41467-021-21511-x · Cited by 243 · see citing works
Crystallographic ab initio protein structure solution below atomic resolution
Rodríguez, D. D., Grosse, C., Himmel, S., González, C., de Ilarduya, I. M., Becker, S., Sheldrick, G. M., & Usón, I. (2009) · Nature Methods · doi:10.1038/nmeth.1365 · Cited by 170 · see citing works
phenix.mr_rosetta: molecular replacement and model rebuilding with Phenix and Rosetta
Terwilliger, T. C., DiMaio, F., Read, R. J., Baker, D. A., Bunkòczi, G., Adams, P. D., Grosse‐Kunstleve, R. W., Afonine, P. V., & Echols, N. (2012) · Journal of Structural and Functional Genomics · doi:10.1007/s10969-012-9129-3 · Cited by 145 · see citing works
Self-citationStructure of the peptidoglycan polymerase RodA resolved by evolutionary coupling analysis
Sjodt, M., Brock, K. P., Dobihal, G. S., Rohs, P. D. A., Green, A. G., Hopf, T. A., Meeske, A. J., Srisuknimit, V., Kahne, D. E., Walker, S., et al. (2018) · Nature · doi:10.1038/nature25985 · Cited by 132 · see citing works
Bibby, J., Keegan, R., Mayans, O., Winn, M., & Rigden, D. (2012) · Acta Crystallographica Section D: Biological Crystallography · doi:10.1107/s0907444912039194 · Cited by 101 · see citing works
The structural basis of fatty acid elongation by the ELOVL elongases
Nie, L., Pascoa, T. C., Pike, A. C. W., Bushell, S. R., Quigley, A., Ruda, G. F., Chu, A., Cole, V., Speedman, D., Moreira, T., et al. (2021) · Nature Structural & Molecular Biology · doi:10.1038/s41594-021-00605-6 · Cited by 94 · see citing works
CaspR: a web server for automated molecular replacement using homology modelling
Claude, J., Suhre, K., Notredame, C., Claverie, J., & Abergel, C. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh400 · Cited by 93 · see citing works
Terwilliger, T. C., Grosse-Kunstleve, R. W., Afonine, P. V., et al. (2008) · PubMed · doi:10.17863/cam.52329 · Cited by 92 · see citing works
Garcia‐Doval, C., Schwede, F., Berk, C., Rostøl, J. T., Niewoehner, O., Tejero, O., Hall, J., Marraffini, L. A., & Jínek, M. (2020) · Nature Communications · doi:10.1038/s41467-020-15334-5 · Cited by 91 · see citing works
Read, R. J., & McCoy, A. J. (2016) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798315013236 · Cited by 67 · see citing works
Self-citationStructural basis for Ca2+-dependent activation of a plant metacaspase
Zhu, P., Yu, X., Wang, C., Zhang, Q., Liu, W., McSweeney, S. M., Shanklin, J., Lam, E., & Liu, Q. (2020) · Nature Communications · doi:10.1038/s41467-020-15830-8 · Cited by 65 · see citing works
HELANAL-Plus: a web server for analysis of helix geometry in protein structures
Kumar, P., & Bansal, M. (2012) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2012.689705 · Cited by 65 · see citing works
Assessing the utility of <scp>CASP14</scp> models for molecular replacement
Millán, C., Keegan, R. M., Pereira, J., Sammito, M. D., Simpkin, A. J., McCoy, A. J., Lupas, A. N., Hartmann, M. D., Rigden, D. J., & Read, R. J. (2021) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.26214 · Cited by 62 · see citing works
Self-citationMolecular replacement then and now
Scapin, G. (2013) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444913011426 · Cited by 61 · see citing works
ARCIMBOLDO_LITE: single-workstation implementation and use
Sammito, M. D., Millán, C., Frieske, D., et al. (2015) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s1399004715010846 · Cited by 61 · see citing works
Self-citationAb initio solution of macromolecular crystal structures without direct methods
McCoy, A. J., Oeffner, R. D., Wrobel, A. G., Ojala, J. R. M., Tryggvason, K., Lohkamp, B., & Read, R. J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1701640114 · Cited by 60 · see citing works
Self-citationFunctional genetic encoding of sulfotyrosine in mammalian cells
He, X., Chen, Y., Beltran, D. G., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18629-9 · Cited by 49 · see citing works
Caballero, I., Sammito, M. D., Millán, C., et al. (2018) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798317017582 · Cited by 49 · see citing works
Self-citationCrystallographic molecular replacement using an in silico‐generated search model of SARS‐CoV‐2 ORF8
Flower, T. G., & Hurley, J. H. (2021) · Protein Science · doi:10.1002/pro.4050 · Cited by 49 · see citing works
Evaluation of template-based modeling in CASP13
Croll, T., Sammito, M., Kryshtafovych, A., & Read, R. J. (2019) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.25800 · Cited by 48 · see citing works
Self-citationStructure solution with ARCIMBOLDO using fragments derived from distant homology models
Sammito, M. D., Meindl, K., de Ilarduya, I. M., et al. (2014) · FEBS Journal · doi:10.1111/febs.12897 · Cited by 46 · see citing works
Self-citationKryshtafovych, A., Moult, J., Albrecht, R., Chang, G. A., Chao, K., Fraser, A., Greenfield, J., Hartmann, M. D., Herzberg, O., Josts, I., et al. (2021) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.26223 · Cited by 45 · see citing works
Structure and function of virion RNA polymerase of a crAss-like phage
Drobysheva, A. V., Panafidina, S. A., Kolesnik, M. V., Klimuk, E. I., Minakhin, L., Yakunina, M. V., Borukhov, S., Nilsson, E., Holmfeldt, K., Yutin, N., et al. (2021) · Nature · doi:10.1038/s41586-020-2921-5 · Cited by 44 · see citing works
On the application of the expected log-likelihood gain to decision making in molecular replacement
Oeffner, R. D., Afonine, P. V., Millán, C., Sammito, M. D., Usón, I., Read, R. J., & McCoy, A. J. (2018) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798318004357 · Cited by 39 · see citing works
Self-citationWang, Y., Virtanen, J., Xue, Z., & Zhang, Y. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx349 · Cited by 38 · see citing works
Millán, C., Sammito, M. D., McCoy, A. J., et al. (2018) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798318001365 · Cited by 32 · see citing works
Self-citation“The structure of the Type III secretion system export gate with CdsO, an ATPase lever arm”
Jensen, J. L., Yamini, S., Rietsch, A., et al. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008923 · Cited by 30 · see citing works
Chen, K., Birkinshaw, R. W., Gurzau, A. D., Wanigasuriya, I., Wang, R., Iminitoff, M., Sandow, J. J., Young, S. N., Hennessy, P. J., Willson, T. A., et al. (2020) · Science Signaling · doi:10.1126/scisignal.aaz5599 · Cited by 26 · see citing works
Routine phasing of coiled-coil protein crystal structures withAMPLE
Thomas, J. M. H., Keegan, R. M., Bibby, J., Winn, M., Mayans, O. M., & Rigden, D. J. (2015) · IUCrJ · doi:10.1107/s2052252515002080 · Cited by 23 · see citing works
Eckenroth, B. E., Cao, V. B., Averill, A. M., et al. (2020) · Structure · doi:10.1016/j.str.2020.08.001 · Cited by 22 · see citing works
Bahat, Y., Alter, J., & Dessau, M. A. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2004657117 · Cited by 20 · see citing works
Bunkóczi, G., Wallner, B., & Read, R. J. (2015) · Structure · doi:10.1016/j.str.2014.11.020 · Cited by 19 · see citing works
Self-citationAdvances inRosettastructure prediction for difficult molecular-replacement problems
DiMaio, F. (2013) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444913023305 · Cited by 17 · see citing works
Google’s DeepMind aces protein folding
Service, R. F. (2018) · Science · doi:10.1126/science.aaw2747 · Cited by 16 · see citing works
A cryptic tubulin-binding domain links MEKK1 to curved tubulin protomers
Filipčík, P., Latham, S. L., Cadell, A. L., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2006429117 · Cited by 16 · see citing works
Molecular replacement using structure predictions from databases
Simpkin, A. J., Thomas, J. M. H., Šimkovic, F., Keegan, R. M., & Rigden, D. J. (2019) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798319013962 · Cited by 15 · see citing works
Insight into the RssB-Mediated Recognition and Delivery of σs to the AAA+ Protease, ClpXP
Micevski, D., Zeth, K., Mulhern, T. D., Schuenemann, V. J., Zammit, J. E., Truscott, K. N., & Dougan, D. A. (2020) · Biomolecules · doi:10.3390/biom10040615 · Cited by 14 · see citing works
Phasertng: directed acyclic graphs for crystallographic phasing
McCoy, A. J., Stockwell, D. H., Sammito, M. D., Oeffner, R. D., Hatti, K. S., Croll, T. I., & Read, R. J. (2020) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798320014746 · Cited by 13 · see citing works
Self-citationMultidimensional molecular replacement
Glykos, N. M., & Kokkinidis, M. (2001) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444901008563 · Cited by 13 · see citing works
Gandini, R., Reichenbach, T., Oliver Spadiut, A., Tan, T.-C., Kalyani, D. C., & Divne, C. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.06.016 · Cited by 12 · see citing works
Structure of the Regulatory Cytosolic Domain of a Eukaryotic Potassium-Chloride Cotransporter
Zimanyi, C. M., Guo, M., Mahmood, A., et al. (2020) · Structure · doi:10.1016/j.str.2020.06.009 · Cited by 10 · see citing works
Molecular-replacement phasing using predicted protein structures from AWSEM-Suite
Jin, S., Miller, M. D., Chen, M., Schafer, N. P., Lin, X., Chen, X., Phillips, G. N., & Wolynes, P. G. (2020) · IUCrJ · doi:10.1107/s2052252520013494 · Cited by 10 · see citing works
Rigden, D., Thomas, J. M. H., Simkovic, F., Simpkin, A., Winn, M., Mayans, O., & Keegan, R. (2018) · Acta Crystallographica Section D: Structural Biology · doi:10.1107/s2059798318002310 · Cited by 7 · see citing works
Crystal structure of the FYCO1 RUN domain suggests possible interfaces with small GTPases
Sakurai, S., Shimizu, T., & Ohto, U. (2020) · Acta Crystallographica Section F Structural Biology Communications · doi:10.1107/s2053230x20009012 · Cited by 6 · see citing works
Factors influencing estimates of coordinate error for molecular replacement
Hatti, K. S., McCoy, A. J., Oeffner, R. D., et al. (2019) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798319015730 · Cited by 5 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 4
- Blundell, T. L. & Johnson, L. N. (1976). Protein Crystallography. New York: Academic Press.
- Ewald, P. P. (1962). Fifty Years of X-ray Diffraction. Boston: Springer.
- Flower, T. G. & Hurley, J. H. (2021). Protein Sci. 30, 728–734. PMC7980513 33625752
- Jäger, F., Lamy, A., Guerini, N., Sun, W.-S. & Berntsson, R. P. A. (2020). bioRxiv, 2020.10.30.342212.
Cited by
Sorted by citations
The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins
Agarwal, V., & McShan, A. C. (2024) · Nature Chemical Biology · doi:10.1038/s41589-024-01638-w · Cited by 155 · see citing works
Ins and outs of AlphaFold2 transmembrane protein structure predictions
Hegedűs, T., Geisler, M., Lukács, G. L., & Farkas, B. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04112-1 · Cited by 127 · see citing works
AlphaFold 2 and NMR Spectroscopy: Partners to Understand Protein Structure, Dynamics and Function
Laurents, D. V. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.906437 · Cited by 95 · see citing works
Putting <i>AlphaFold</i> models to work with <i>phenix.process_predicted_model</i> and <i>ISOLDE</i>
Oeffner, R. D., Croll, T. I., Millán, C., Poon, B. K., Schlicksup, C. J., Read, R. J., & Terwilliger, T. C. (2022) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798322010026 · Cited by 63 · see citing works
Self-citationAccelerating crystal structure determination with iterative <i>AlphaFold</i> prediction
Terwilliger, T. C., Afonine, P. V., Liebschner, D., Croll, T. I., McCoy, A. J., Oeffner, R. D., Williams, C. J., Poon, B. K., Richardson, J. S., Read, R. J., et al. (2023) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s205979832300102x · Cited by 62 · see citing works
Self-citationAssessing the utility of <scp>CASP14</scp> models for molecular replacement
Millán, C., Keegan, R. M., Pereira, J., Sammito, M. D., Simpkin, A. J., McCoy, A. J., Lupas, A. N., Hartmann, M. D., Rigden, D. J., & Read, R. J. (2021) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.26214 · Cited by 62 · see citing works
Self-citationBarbarin-Bocahu, I., & Graille, M. (2022) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798322002157 · Cited by 52 · see citing works
Varadi, M., Bordin, N., Orengo, C., & Velankar, S. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102543 · Cited by 29 · see citing works
Brookes, E., Rocco, M., Vachette, P., & Trewhella, J. (2023) · Journal of Applied Crystallography · doi:10.1107/s1600576723005344 · Cited by 21 · see citing works
Thorn, A. (2022) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2022.102368 · Cited by 16 · see citing works
- Authors
- McCoy, A. J., Sammito, M. D., & Read, R. J.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- McCoy, Airlie J.
- Venue
- Acta Crystallographica Section D Structural Biology
- Published
- 2022-01-01
- Volume
- 78
- Issue
- 1
- Pages
- 1-13
- ISSN
- 2059-7983 (ISSN-L)
- PMC
- PMC8725160
- OpenAlex
- W4200268506
- Cited by
- 104
- References
- 58
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 23 · 2023: 38 · 2022: 22 · 2021: 6
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Acta Crystallographica Section D Structural Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (209407/Z/17/Z)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Chemistry › Inorganic Chemistry › Crystal structures of chemical compounds
- Keywords
- AlphaFold2, crystallographic phasing, molecular replacement, CASP14, protein structure prediction, deep learning, correlated mutations
- MeSH terms
- Deep Learning, Animals, Computer Simulation, Humans, Models, Molecular, Protein Conformation, Software, Molecular Structure, Crystallography, X-Ray, Computational Biology
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
