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AlphaFold Models of Small Proteins Rival the Accuracy of Solution NMR Structures
Recent advances in molecular modeling using deep learning have the potential to revolutionize the field of structural biology. In particular, AlphaFold has been observed to provide models of protein structures with accuracies rivaling medium-resolution X-ray crystal structures, and with excellent at...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234698/ https://www.ncbi.nlm.nih.gov/pubmed/35769913 http://dx.doi.org/10.3389/fmolb.2022.877000 |
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author | Tejero, Roberto Huang, Yuanpeng Janet Ramelot, Theresa A. Montelione, Gaetano T. |
author_facet | Tejero, Roberto Huang, Yuanpeng Janet Ramelot, Theresa A. Montelione, Gaetano T. |
author_sort | Tejero, Roberto |
collection | PubMed |
description | Recent advances in molecular modeling using deep learning have the potential to revolutionize the field of structural biology. In particular, AlphaFold has been observed to provide models of protein structures with accuracies rivaling medium-resolution X-ray crystal structures, and with excellent atomic coordinate matches to experimental protein NMR and cryo-electron microscopy structures. Here we assess the hypothesis that AlphaFold models of small, relatively rigid proteins have accuracies (based on comparison against experimental data) similar to experimental solution NMR structures. We selected six representative small proteins with structures determined by both NMR and X-ray crystallography, and modeled each of them using AlphaFold. Using several structure validation tools integrated under the Protein Structure Validation Software suite (PSVS), we then assessed how well these models fit to experimental NMR data, including NOESY peak lists (RPF-DP scores), comparisons between predicted rigidity and chemical shift data (ANSURR scores), and (15)N-(1)H residual dipolar coupling data (RDC Q factors) analyzed by software tools integrated in the PSVS suite. Remarkably, the fits to NMR data for the protein structure models predicted with AlphaFold are generally similar, or better, than for the corresponding experimental NMR or X-ray crystal structures. Similar conclusions were reached in comparing AlphaFold2 predictions and NMR structures for three targets from the Critical Assessment of Protein Structure Prediction (CASP). These results contradict the widely held misperception that AlphaFold cannot accurately model solution NMR structures. They also document the value of PSVS for model vs. data assessment of protein NMR structures, and the potential for using AlphaFold models for guiding analysis of experimental NMR data and more generally in structural biology. |
format | Online Article Text |
id | pubmed-9234698 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92346982022-06-28 AlphaFold Models of Small Proteins Rival the Accuracy of Solution NMR Structures Tejero, Roberto Huang, Yuanpeng Janet Ramelot, Theresa A. Montelione, Gaetano T. Front Mol Biosci Molecular Biosciences Recent advances in molecular modeling using deep learning have the potential to revolutionize the field of structural biology. In particular, AlphaFold has been observed to provide models of protein structures with accuracies rivaling medium-resolution X-ray crystal structures, and with excellent atomic coordinate matches to experimental protein NMR and cryo-electron microscopy structures. Here we assess the hypothesis that AlphaFold models of small, relatively rigid proteins have accuracies (based on comparison against experimental data) similar to experimental solution NMR structures. We selected six representative small proteins with structures determined by both NMR and X-ray crystallography, and modeled each of them using AlphaFold. Using several structure validation tools integrated under the Protein Structure Validation Software suite (PSVS), we then assessed how well these models fit to experimental NMR data, including NOESY peak lists (RPF-DP scores), comparisons between predicted rigidity and chemical shift data (ANSURR scores), and (15)N-(1)H residual dipolar coupling data (RDC Q factors) analyzed by software tools integrated in the PSVS suite. Remarkably, the fits to NMR data for the protein structure models predicted with AlphaFold are generally similar, or better, than for the corresponding experimental NMR or X-ray crystal structures. Similar conclusions were reached in comparing AlphaFold2 predictions and NMR structures for three targets from the Critical Assessment of Protein Structure Prediction (CASP). These results contradict the widely held misperception that AlphaFold cannot accurately model solution NMR structures. They also document the value of PSVS for model vs. data assessment of protein NMR structures, and the potential for using AlphaFold models for guiding analysis of experimental NMR data and more generally in structural biology. Frontiers Media S.A. 2022-06-13 /pmc/articles/PMC9234698/ /pubmed/35769913 http://dx.doi.org/10.3389/fmolb.2022.877000 Text en Copyright © 2022 Tejero, Huang, Ramelot and Montelione. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Tejero, Roberto Huang, Yuanpeng Janet Ramelot, Theresa A. Montelione, Gaetano T. AlphaFold Models of Small Proteins Rival the Accuracy of Solution NMR Structures |
title | AlphaFold Models of Small Proteins Rival the Accuracy of Solution NMR Structures |
title_full | AlphaFold Models of Small Proteins Rival the Accuracy of Solution NMR Structures |
title_fullStr | AlphaFold Models of Small Proteins Rival the Accuracy of Solution NMR Structures |
title_full_unstemmed | AlphaFold Models of Small Proteins Rival the Accuracy of Solution NMR Structures |
title_short | AlphaFold Models of Small Proteins Rival the Accuracy of Solution NMR Structures |
title_sort | alphafold models of small proteins rival the accuracy of solution nmr structures |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234698/ https://www.ncbi.nlm.nih.gov/pubmed/35769913 http://dx.doi.org/10.3389/fmolb.2022.877000 |
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