Consistent blind protein structure generation from NMR chemical shift data
Open accessAbstract
Protein NMR chemical shifts are highly sensitive to local structure. A robust protocol is described that exploits this relation for de novo protein structure generation, using as input experimental parameters the 13 C α , 13 C β , 13 C′, 15 N, 1 H α and 1 H N NMR chemical shifts. These shifts are generally available at the early stage of the traditional NMR structure determination process, before the collection and analysis of structural restraints. The chemical shift based structure determination protocol uses an empirically optimized procedure to select protein fragments from the Protein Data Bank, in conjunction with the standard ROSETTA Monte Carlo assembly and relaxation methods. Evaluation of 16 proteins, varying in size from 56 to 129 residues, yielded full-atom models that have 0.7–1.8 Å root mean square deviations for the backbone atoms relative to the experimentally determined x-ray or NMR structures. The strategy also has been successfully applied in a blind manner to nine protein targets with molecular masses up to 15.4 kDa, whose conventional NMR structure determination was conducted in parallel by the Northeast Structural Genomics Consortium. This protocol potentially provides a new direction for high-throughput NMR structure determination.
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CS-Rosetta models calculated from KaiBTV-4 chemical shifts are within 1.8 ± 0.3 Å r.m.s.d. to the FS state predicted by AF-cluster.
“CS-Rosetta39 models calculated from the chemical shifts (Fig. 2e) are within 1.8 ± 0.3 Å r.m.s.d. to the FS state predicted by AF-cluster.”
From Predicting multiple conformations via sequence clustering and AlphaFold2 (2024) · cites this paper as [39]
Cites
Equation of State Calculations by Fast Computing Machines
Metropolis, N., Rosenbluth, A. W., Rosenbluth, M. N., Teller, A. H., & Teller, E. (1953) · The Journal of Chemical Physics · doi:10.1063/1.1699114 · Cited by 37,192 · see citing works
Kabsch, W., & Sander, C. (1983) · Biopolymers · doi:10.1002/bip.360221211 · Cited by 15,320 · see citing works
MOLMOL: A program for display and analysis of macromolecular structures
Koradi, R., Billeter, M., & Kurt Wüthrich, A. (1996) · Journal of Molecular Graphics · doi:10.1016/0263-7855(96)00009-4 · Cited by 7,163 · see citing works
AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMR
Laskowski, R., Rullmann, J. A., MacArthur, M., Kaptein, R., & Thornton, J. (1996) · Journal of Biomolecular NMR · doi:10.1007/bf00228148 · Cited by 5,502 · see citing works
Protein backbone angle restraints from searching a database for chemical shift and sequence homology
Cornilescu, G., Delaglio, F., & Bax, A. (1999) · Journal of Biomolecular NMR · doi:10.1023/a:1008392405740 · Cited by 2,957 · see citing works
Tjandra, N., & Bax, A. (1997) · Science · doi:10.1126/science.278.5340.1111 · Cited by 1,720 · see citing works
Self-citationProtein Structure Prediction Using Rosetta
Rohl, C. A., Strauss, C. E. M., Misura, K. M. S., & Baker, D. A. (2004) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(04)83004-0 · Cited by 1,711 · see citing works
Self-citationPISCES: a protein sequence culling server
Wang, G., & Dunbrack, R. L. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btg224 · Cited by 1,664 · see citing works
Word, J. M., Lovell, S. C., Richardson, J. S., & Richardson, D. C. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.2401 · Cited by 1,432 · see citing works
Simons, K. T., Kooperberg, C. L., Huang, E. S., & Baker, D. A. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.0959 · Cited by 1,387 · see citing works
Self-citationTHE KINETICS OF FORMATION OF NATIVE RIBONUCLEASE DURING OXIDATION OF THE REDUCED POLYPEPTIDE CHAIN
Anfinsen, C. B., Haber, E., Sela, M., & White, F. H. (1961) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.47.9.1309 · Cited by 1,182 · see citing works
Toward High-Resolution de Novo Structure Prediction for Small Proteins
Bradley, P. H., Misura, K. M. S., & Baker, D. A. (2005) · Science · doi:10.1126/science.1113801 · Cited by 865 · see citing works
Self-citationTolman, J. R., Flanagan, J. M., Kennedy, M. A., et al. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9279 · Cited by 838 · see citing works
Native protein sequences are close to optimal for their structures
Kuhlman, B. A., & Baker, D. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.19.10383 · Cited by 814 · see citing works
Self-citationBayesian statistical analysis of protein side‐chain rotamer preferences
Dunbrack, R. L., & Cohen, F. E. (1997) · Protein Science · doi:10.1002/pro.5560060807 · Cited by 776 · see citing works
Protein structure determination from NMR chemical shifts
Cavalli, A., Salvatella, X., Dobson, C. M., & Vendruscolo, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610313104 · Cited by 557 · see citing works
Rapid and accurate calculation of protein 1H, 13C and 15N chemical shifts
Neal, S., Nip, A. M., Zhang, H., & Wishart, D. S. (2003) · Journal of Biomolecular NMR · doi:10.1023/a:1023812930288 · Cited by 540 · see citing works
Hydrogen bond length and proton NMR chemical shifts in proteins
Wagner, G. H., Pardi, A., & Wuethrich, K. (1983) · Journal of the American Chemical Society · doi:10.1021/ja00356a056 · Cited by 401 · see citing works
Shen, Y., & Bax, A. (2007) · Journal of Biomolecular NMR · doi:10.1007/s10858-007-9166-6 · Cited by 362 · see citing works
Self-citationXu, X.-P., & Case, D. A. (2001) · Journal of Biomolecular NMR · doi:10.1023/a:1013324104681 · Cited by 269 · see citing works
Huang, Y. J., Powers, R., & Montelione, G. T. (2005) · Journal of the American Chemical Society · doi:10.1021/ja047109h · Cited by 253 · see citing works
Self-citationProtein Structure Determination Using Molecular Fragment Replacement and NMR Dipolar Couplings
Delaglio, F., Kontaxis, G., & Bax, A. (2000) · Journal of the American Chemical Society · doi:10.1021/ja993603n · Cited by 250 · see citing works
Self-citationNew methods for fast multidimensional NMR
Freeman, R., & Kupče, Ē. (2003) · Journal of Biomolecular NMR · doi:10.1023/a:1024960302926 · Cited by 185 · see citing works
De novo protein structure determination using sparse NMR data
Bowers, P. M., Strauss, C. E. M., & Baker, D. A. (2000) · Journal of Biomolecular NMR · doi:10.1023/a:1026744431105 · Cited by 181 · see citing works
Self-citationAn improved protein decoy set for testing energy functions for protein structure prediction
Tsai, J., Bonneau, R., Morozov, A. V., Kuhlman, B., Rohl, C. A., & Baker, D. (2003) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.10454 · Cited by 158 · see citing works
Self-citationEmpirical Comparisons of Models for Chemical-Shift Calculation in Proteins
Williamson, M. P., & Asakura, T. (1993) · Journal of Magnetic Resonance Series B · doi:10.1006/jmrb.1993.1008 · Cited by 157 · see citing works
Progress and challenges in high‐resolution refinement of protein structure models
Misura, K. M. S., & Baker, D. A. (2005) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20376 · Cited by 153 · see citing works
Self-citationAlmeida, M. S., Johnson, M. A., Herrmann, T., Geralt, M., & Kurt Wüthrich, A. (2007) · Journal of Virology · doi:10.1128/jvi.01939-06 · Cited by 136 · see citing works
Robotic cloning and protein production platform of the northeast structural genomics consortium
Acton, T. B., Gunsalus, K. C., Xiao, R., Ma, L. C., Aramini, J., Baran, M. C., Chiang, Y.-W., Climent, T., Cooper, B., Denissova, N. G., et al. (2005) · Methods in Enzymology · doi:10.1016/s0076-6879(05)94008-1 · Cited by 129 · see citing works
Self-citationNMR data collection and analysis protocol for high-throughput protein structure determination
Liu, G., Shen, Y., Atreya, H. S., Parish, D., Shao, Y., Sukumaran, D. K., Xiao, R., Yee, A. A., Lemak, A. S., Bhattacharya, A., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504338102 · Cited by 117 · see citing works
Self-citationCalibration of ring-current effects in proteins and nucleic acids
Case, D. A. (1995) · Journal of Biomolecular NMR · doi:10.1007/bf00197633 · Cited by 105 · see citing works
Atreya, H. S., & Szyperski, T. (2005) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(05)94004-4 · Cited by 90 · see citing works
Self-citationNMR: prediction of protein flexibility
Berjanskii, M. V., & Wishart, D. S. (2006) · Nature Protocols · doi:10.1038/nprot.2006.108 · Cited by 86 · see citing works
Exploring steric constraints on protein mutations using MAGE/PROBE
Word, J. M., Presley, B. K., Lovell, S. C., Richardson, D. C., & Batemanm, R. C. (2000) · Protein Science · doi:10.1110/ps.9.11.2251 · Cited by 72 · see citing works
Tertiary and quaternary conformational changes in aspartate transcarbamylase: a normal mode study
Thomas, A. M., Hinsen, K., Field, M. J., & Pérahia, D. (1999) · Proteins Structure Function and Bioinformatics · doi:10.1002/(sici)1097-0134(19990101)34:1 · Cited by 64 · see citing works
Kontaxis, G., Delaglio, F., & Bax, A. (2005) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(05)94003-2 · Cited by 59 · see citing works
Self-citationDoreleijers, J. F., Nederveen, A. J., Vranken, W., et al. (2005) · Journal of Biomolecular NMR · doi:10.1007/s10858-005-2195-0 · Cited by 52 · see citing works
Gong, H., Shen, Y., & Rose, G. D. (2007) · Protein Science · doi:10.1110/ps.072988407 · Cited by 35 · see citing works
Self-citationABACUS, a direct method for protein NMR structure computation via assembly of fragments
Grishaev, A., Steren, C. A., Wu, B., et al. (2005) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20457 · Cited by 33 · see citing works
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Goh, G. B., Hodas, N. O., & Vishnu, A. (2017) · Journal of Computational Chemistry · doi:10.1002/jcc.24764 · Cited by 809 · see citing works
Predicting multiple conformations via sequence clustering and AlphaFold2
Wayment-Steele, H. K., Ojoawo, A., Otten, R., Apitz, J. M., Pitsawong, W., Hömberger, M., Ovchinnikov, S., Colwell, L., & Kern, D. (2024) · Nature · doi:10.1038/s41586-023-06832-9 · Cited by 545 · see citing works
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Brzovic, P. S., Heikaus, C. C., Kisselev, L., Vernon, R., Herbig, E., Pacheco, D., Warfield, L., Littlefield, P., Baker, D., Klevit, R. E., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.11.008 · Cited by 203 · see citing works
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Streit, J. O., Chan, S. H. S., Daya, S., & Christodoulou, J. (2025) · Nature Communications · doi:10.1038/s41467-025-59105-6 · Cited by 17 · see citing works
- Authors
- Shen, Y., Lange, O., Delaglio, F., Rossi, P., Aramini, J. M., Liu, G., Eletsky, A., Wu, Y., Singarapu, K. K., Lemak, A., Ignatchenko, A., Arrowsmith, C. H., Szyperski, T., Montelione, G. T., Baker, D., & Bax, A.
- Affiliations
- National Institutes of Health (US)
- Howard Hughes Medical Institute (US)
- Rutgers, The State University of New Jersey (US)
- University at Buffalo, State University of New York (US)
- University of Toronto (CA)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-03-25
- Volume
- 105
- Issue
- 12
- Pages
- 4685-4690
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2290745
- OpenAlex
- W2011148270
- Cited by
- 855
- References
- 39
- Citations by year
- 2026: 18 · 2025: 23 · 2024: 25 · 2023: 22 · 2022: 23 · 2021: 28 · 2020: 30 · 2019: 37 · 2018: 42 · 2017: 43 · 2016: 33 · 2015: 60 · 2014: 81 · 2013: 70 · 2012: 80
- FWCI
- 32.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of General Medical Sciences (U54GM074958)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Chemistry › Spectroscopy › Advanced NMR Techniques and Applications
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- protein structure generation, NMR chemical shifts, Rosetta, structural genomics, backbone conformation
- MeSH terms
- Models, Molecular, Magnetic Resonance Spectroscopy, Proteins, Software, Thermodynamics, Protein Structure, Secondary, Genomics, Ubiquitin
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