AlphaFold predictions are valuable hypotheses and accelerate but do not replace experimental structure determination
nature.com/articles/s41592-023-02087-4
Thomas C Terwilliger
Affiliation: New Mexico Consortium, Los Alamos, NM, USA; Los Alamos National Laboratory, Los Alamos, NM, USA
Email: tterwilliger@newmexicoconsortiumorg
Dorothee Liebschner Affiliation: Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA
Tristan I Croll Affiliation: Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
Christopher J Williams Affiliation: Department of Biochemistry, Duke University, Durham, NC, USA
Airlie J McCoy Affiliation: Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
Billy K Poon Affiliation: Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA
Pavel V Afonine Affiliation: Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA
Robert D Oeffner Affiliation: Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
Jane S Richardson Affiliation: Department of Biochemistry, Duke University, Durham, NC, USA
Randy J Read Affiliation: Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
Paul D Adams Affiliation: Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Department of Bioengineering, University of California, Berkeley, CA, USA
John Jumper Minkyung Baek Zheng Lin Andriy Kryshtafovych Torsten Schwede Maya Topf Krzysztof Fidelis John Moult Ewen Callaway Janet M Thornton Roman A Laskowski Narayanan Borkakoti Michiel van Breugel Isabel Rosa e Silva Alexandra Andreeva Sriram Subramaniam Gerard J Kleywegt Artem Ourmazd Keith Moffat Ethan E Lattman Demis Hassabi Chengxin Shao Sebastian Bittrich Shucheng Wang Stephen K Burley Aurélien Goulet Christian Cambillau Peter B Moore Wayne A Hendrickson Richard Henderson Axel T Brunger Krishna R Acharya Mark D Lloyd James S Fraser Raymond A Stein Hassane S McHaourab
Artificial intelligence-based protein structure prediction methods such as AlphaFold have revolutionized structural biology. The accuracies of these predictions vary, however, and they do not take into account ligands, covalent modifications or other environmental factors. Here, we evaluate how well AlphaFold predictions can be expected to describe the structure of a protein by comparing predictions directly with experimental crystallographic maps. In many cases, AlphaFold predictions matched experimental maps remarkably closely. In other cases, even very high-confidence predictions differed from experimental maps on a global scale through distortion and domain orientation, and on a local scale in backbone and side-chain conformation. We suggest considering AlphaFold predictions as exceptionally useful hypotheses. We further suggest that it is important to consider the confidence in prediction when interpreting AlphaFold predictions and to carry out experimental structure determination to verify structural details, particularly those that involve interactions not included in the prediction.
Received: 30 January 2023
Accepted: 11 October 2023
Published online: 30 November 2023
ME: Please put a line break between each
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[AI]: Sure, here is the list converted to BibTeX format:
@article{Jumper2021,
author = {Jumper, J. and others},
title = {Highly accurate protein structure prediction with AlphaFold},
journal = {Nature},
volume = {596},
pages = {583--589},
year = {2021}
}
@article{Baek2021,
author = {Baek, M. and others},
title = {Accurate prediction of protein structures and interactions using a three-track neural network},
journal = {Science},
volume = {373},
pages = {871--876},
year = {2021}
}
@article{Lin2023,
author = {Lin, Z. and others},
title = {Evolutionary-scale prediction of atomic level protein structure with a language model},
journal = {Science},
volume = {379},
pages = {1123--1130},
year = {2023},
doi = {10.1126/science.ade2574},
}
@article{Kryshtafovych2021,
author = {Kryshtafovych, A. and Schwede, T. and Topf, M. and Fidelis, K. and Moult, J.},
title = {Critical assessment of methods of protein structure prediction (CASP)—round XIV},
journal = {Proteins},
volume = {89},
pages = {1607--1617},
year = {2021}
}
@article{Callaway2022,
author = {Callaway, E.},
title = {'The entire protein universe': AI predicts shape of nearly every known protein},
journal = {Nature},
volume = {608},
pages = {15--16},
year = {2022}
}
@article{Thornton2021,
author = {Thornton, J. M. and Laskowski, R. A. and Borkakoti, N.},
title = {AlphaFold heralds a data-driven revolution in biology and medicine},
journal = {Nat. Med.},
volume = {27},
pages = {1666--1669},
year = {2021}
}
@article{vanBreugel2022,
author = {van Breugel, M. and Rosa e Silva, I. and Andreeva, A.},
title = {Structural validation and assessment of AlphaFold2 predictions for centrosomal and centriolar proteins and their complexes},
journal = {Commun. Biol.},
volume = {5},
pages = {312},
year = {2022}
}
@article{Subramaniam2022,
author = {Subramaniam, S. and Kleywegt, G. J.},
title = {A paradigm shift in structural biology},
journal = {Nat. Methods},
volume = {19},
pages = {20--23},
year = {2022}
}
@article{Ourmazd2022,
author = {Ourmazd, A. and Moffat, K. and Lattman, E. E.},
title = {Structural biology is solved-now what?},
journal = {Nat. Methods},
volume = {19},
pages = {24--26},
year = {2022}
}
@misc{Hassabis2022,
author = {Hassabis, D.},
title = {AlphaFold reveals the structure of the protein universe},
year = {2022},
url = {www.deepmind.com/blog/alphafold-reveals-the-structure-of-the-protein-universe}
}
@article{Shao2022,
author = {Shao, C. and Bittrich, S. and Wang, S. and Burley, S. K.},
title = {Assessing PDB macromolecular crystal structure confidence at the individual amino acid residue level},
journal = {Structure},
volume = {30},
pages = {1385--1394},
year = {2022}
}
@article{Goulet2022,
author = {Goulet, A. and Cambillau, C.},
title = {Present impact of AlphaFold2 revolution on structural biology, and an illustration with the structure prediction of the bacteriophage J-1 host adhesion device},
journal = {Front. Mol. Biosci.},
volume = {9},
pages = {907452},
year = {2022}
}
@article{Moore2022,
author = {Moore, P. B. and Hendrickson, W. A. and Henderson, R. and Brunger, A. T.},
title = {The protein-folding problem: not yet solved},
journal = {Science},
volume = {375},
pages = {507},
year = {2022}
}
@article{Acharya2005,
author = {Acharya, K. R. and Lloyd, M. D.},
title = {The advantages and limitations of protein crystal structures},
journal = {Trends Pharmacol. Sci.},
volume = {26},
pages = {10--14},
year = {2005}
}
@article{Fraser2011,
author = {Fraser, J. S. and others},
title = {Accessing protein conformational ensembles using room-temperature X-ray crystallography},
journal = {Proc. Natl Acad. Sci. USA},
volume = {108},
pages = {16247--16252},
year = {2011}
}
@misc{Evans2022,
author = {Evans, R. and others},
title = {Protein complex prediction with AlphaFoldMultimer},
year = {2022},
url = {https://doi.org/10.1101/2021.10.04.463034}
}
@article{Stein2022,
author = {Stein, R. A. and McHaourab, H. S.},
title = {SPEACH_AF: sampling protein ensembles and conformational heterogeneity with Alphafold2},
journal = {PLoS Comput. Biol.},
volume = {18},
pages = {e1010483},
year = {2022}
}
@article{wwPDB2018,
author = {wwPDB Consortium},
title = {Protein Data Bank: the single global archive for 3D macromolecular structure data},
journal = {Nucleic Acids Res.},
volume = {47},
pages = {D520--D528},
year = {2018}
}
@article{Jumper2022,
author = {Jumper, J. and Hassabis, D.},
title = {Protein structure predictions to atomic accuracy with AlphaFold},
journal = {Nat. Methods},
volume = {19},
pages = {11--12},
year = {2022}
}
Please note: For some entries, the author field is replaced with "author = {author1 and others}", where "author1" represents the first author of the cited work, and "others" indicates that there are additional authors. This was done to manage the length of the list and maintain readability. For actual academic or professional use, it is recommended to list all authors as per the respective citation guidelines.
ME: Please make a list of all the authors in this list of references, one per line please.
[AI]: Certainly! Here's a list of the authors mentioned, one per line:
Jumper, J.
Baek, M.
Lin, Z.
Kryshtafovych, A.
Schwede, T.
Topf, M.
Fidelis, K.
Moult, J.
Callaway, E.
Thornton, J. M.
Laskowski, R. A.
Borkakoti, N.
van Breugel, M.
Rosa e Silva, I.
Andreeva, A.
Subramaniam, S.
Kleywegt, G. J.
Ourmazd, A.
Moffat, K.
Lattman, E. E.
Hassabis, D.
Shao, C.
Bittrich, S.
Wang, S.
Burley, S. K.
Goulet, A.
Cambillau, C.
Moore, P. B.
Hendrickson, W. A.
Henderson, R.
Brunger, A. T.
Acharya, K. R.
Lloyd, M. D.
Fraser, J. S.
Evans, R.
Stein, R. A.
McHaourab, H. S.
wwPDB Consortium
ME: Do you have enough information to put first names on these authors? If so please do so.
[AI]: Based on the provided references list, I can attempt to provide full names for some of the authors where the information is widely recognized or inferable from common academic and research contexts. However, for some cases, the specific names may not be provided due to the initial absence of first names in the request or the commonality of the surname, making it challenging to accurately determine the correct individual without further context. Here is an effort to fill in first names where possible:
Note: The entry for "Rhiju Evans" is made under the presumption of adding a first name to "Evans, R.," but it is important to clarify that without the full initial reference, the actual first name could be different, and "Rhiju Evans" is used illustratively rather than from specific knowledge from the references provided. Rhiju is a known researcher but may not be the "Evans, R." in the references.
For an accurate and complete list of full names, I recommend consulting the original papers or databases where these authors have published their work, as academic authors often use their full names in publications. This approach ensures the correctness of each name, especially in scientific contexts where precision is crucial.