Journal of Biomolecular NMR

, Volume 62, Issue 4, pp 473–480 | Cite as

CASD-NMR 2: robust and accurate unsupervised analysis of raw NOESY spectra and protein structure determination with UNIO

  • Paul Guerry
  • Viet Dung Duong
  • Torsten HerrmannEmail author


UNIO is a comprehensive software suite for protein NMR structure determination that enables full automation of all NMR data analysis steps involved—including signal identification in NMR spectra, sequence-specific backbone and side-chain resonance assignment, NOE assignment and structure calculation. Within the framework of the second round of the community-wide stringent blind NMR structure determination challenge (CASD-NMR 2), we participated in two categories of CASD-NMR 2, namely using either raw NMR spectra or unrefined NOE peak lists as input. A total of 15 resulting NMR structure bundles were submitted for 9 out of 10 blind protein targets. All submitted UNIO structures accurately coincided with the corresponding blind targets as documented by an average backbone root mean-square deviation to the reference proteins of only 1.2 Å. Also, the precision of the UNIO structure bundles was virtually identical to the ensemble of reference structures. By assessing the quality of all UNIO structures submitted to the two categories, we find throughout that only the UNIO–ATNOS/CANDID approach using raw NMR spectra consistently yielded structure bundles of high quality for direct deposition in the Protein Data Bank. In conclusion, the results obtained in CASD-NMR 2 are another vital proof for robust, accurate and unsupervised NMR data analysis by UNIO for real-world applications.


Nuclear magnetic resonance Unsupervised data analysis Protein structure determination UNIO ATNOS CANDID CASD-NMR 


  1. Billeter M, Wagner G, Wüthrich K (2008) Solution NMR structure determination of proteins revisited. J Biomol NMR 42:155–158CrossRefGoogle Scholar
  2. Dutta SK, Serrano P, Proudfoot A, Geralt M, Pedrini B, Herrmann T, Wüthrich K (2015) APSY-NMR for protein backbone assignment in high-throughput structural biology. J Biomol NMR 61:47–53. doi: 10.1007/s10858-014-9881-8 CrossRefGoogle Scholar
  3. Fadel V, Bettendorff P, Herrmann T, de Azevedo WF Jr, Oliveira EB, Yamane T, Wüthrich K (2005) Automated NMR structure determination and disulfide bond identification of the myotoxin crotamine from Crotalus durissus terrificus. Toxicon 46:759–767. doi: 10.1016/j.toxicon.2005.07.018 CrossRefGoogle Scholar
  4. Fiorito F, Herrmann T, Damberger FF, Wüthrich K (2008) Automated amino acid side-chain NMR assignment of proteins using C-13- and N-15-resolved 3D [H-1, H-1]-NOESY. J Biomol NMR 42:23–33CrossRefGoogle Scholar
  5. Guerry P, Herrmann T (2011) Advances in automated NMR protein structure determination. Q Rev Biophys 44:257–309CrossRefGoogle Scholar
  6. Guerry P, Herrmann T (2012) Comprehensive automation for NMR structure determination of proteins. Methods Mol Biol 831:429–451. doi: 10.1007/978-1-61779-480-3_22 CrossRefGoogle Scholar
  7. Güntert P (2003) Automated NMR protein structure calculation. Prog Nucl Magn Spectrosc 43:105–125CrossRefGoogle Scholar
  8. Güntert P, Mumenthaler C, Wüthrich K (1997) Torsion angle dynamics for NMR structure calculation with the new program DYANA. J Mol Biol 273:283–298CrossRefGoogle Scholar
  9. Herrmann T, Güntert P, Wüthrich K (2002a) Protein NMR structure determination with automated NOE assignment using the new software CANDID and the torsion angle dynamics algorithm DYANA. J Mol Biol 319:209–227CrossRefGoogle Scholar
  10. Herrmann T, Güntert P, Wüthrich K (2002b) Protein NMR structure determination with automated NOE-identification in the NOESY spectra using the new software ATNOS. J Biomol NMR 24:171–189CrossRefGoogle Scholar
  11. Jaudzems K, Pedrini B, Geralt M, Serrano P, Wüthrich K (2015) J-UNIO protocol used for NMR structure determination of the 206-residue protein NP_346487.1 from streptococcus pneumoniae TIGR4. J Biomol NMR 61:65–72. doi: 10.1007/s10858-014-9886-3 CrossRefGoogle Scholar
  12. Knight MJ, Webber AL, Pell AJ, Guerry P, Barbet-Massin E, Bertini I, Felli IC, Gonnelli L, Pierattelli R, Emsley L, Lesage A, Herrmann T, Pintacuda G (2011) Fast resonance assignment and fold determination of human superoxide dismutase by high-resolution proton-detected solid-state mas nmr spectroscopy. Angew Chem Int Edit 50:11697–11701CrossRefGoogle Scholar
  13. Knight MJ, Pell AJ, Bertini I, Felli IC, Gonnelli L, Pierattelli R, Herrmann T, Emsley L, Pintacuda G (2012) Structure and backbone dynamics of a microcrystalline metalloprotein by solid-state NMR. Proc Natl Acad Sci USA 109:11095–11100CrossRefADSGoogle Scholar
  14. Koradi R, Billeter M, Güntert P (2000) Point-centered domain decomposition for parallel molecular dynamics simulation. Comput Phys Commun 124:139–147CrossRefADSzbMATHGoogle Scholar
  15. Lee W, Kim JH, Westler WM, Markley JL (2011) PONDEROSA, an automated 3D-NOESY peak picking program, enables automated protein structure determination. Bioinformatics 27:1727–1728CrossRefGoogle Scholar
  16. Luginbuhl P, Güntert P, Billeter M, Wüthrich K (1996) The new program OPAL for molecular dynamics simulations and energy refinements of biological macromolecules. J Biomol NMR 8:136–146CrossRefGoogle Scholar
  17. Manolikas T, Herrmann T, Meier BH (2008) Protein structure determination from C-13 spin-diffusion solid-state NMR spectroscopy. J Am Chem Soc 130:3959–3966CrossRefGoogle Scholar
  18. Montelione GT, Nilges M, Bax A, Güntert P, Herrmann T, Richardson JS, Schwieters CD, Vranken WF, Vuister GW, Wishart DS, Berman HM, Kleywegt GJ, Markley JL (2013) Recommendations of the wwPDB NMR validation task force. Structure 21:1563–1570CrossRefGoogle Scholar
  19. ODonoghue SI, King GF, Nilges M (1996) Calculation of symmetric multimer structures from NMR data using a priori knowledge of the monomer structure, co-monomer restraints, and interface mapping: the case of leucine zippers. J Biomol NMR 8:193–206Google Scholar
  20. Ponder JW, Case DA (2003) Force fields for protein simulations. Adv Protein Chem 66:27–85CrossRefGoogle Scholar
  21. Rieping W, Habeck M, Bardiaux B, Bernard A, Malliavin TE, Nilges M (2007) ARIA2: automated NOE assignment and data integration in NMR structure calculation. Bioinformatics 23:381–382CrossRefGoogle Scholar
  22. Rosato A, Bagaria A, Baker D, Bardiaux B, Cavalli A, Doreleijers JF, Giachetti A, Guerry P, Güntert P, Herrmann T, Huang YJ, Jonker HRA, Mao B, Malliavin TE, Montelione GT, Nilges M, Raman S, van der Schot G, Vranken WF, Vuister GW, Bonvin AMJJ (2009) CASD-NMR: critical assessment of automated structure determination by NMR. Nat Methods 6:625–626CrossRefGoogle Scholar
  23. Rosato A, Aramini JM, Arrowsmith C, Bagaria A, Baker D, Cavalli A, Doreleijers JF, Eletsky A, Giachetti A, Guerry P, Gutmanas A, Güntert P, He YF, Herrmann T, Huang YPJ, Jaravine V, Jonker HRA, Kennedy MA, Lange OF, Liu GH, Malliavin TE, Mani R, Mao BC, Montelione GT, Nilges M, Rossi P, van der Schot G, Schwalbe H, Szyperski TA, Vendruscolo M, Vernon R, Vranken WF, de Vries S, Vuister GW, Wu B, Yang YH, Bonvin AMJJ (2012) Blind testing of routine fully automated determination of protein structures from NMR data. Structure 20:227–236CrossRefGoogle Scholar
  24. Serrano P, Pedrini B, Mohanty B, Geralt M, Herrmann T, Wüthrich K (2012) The J-UNIO protocol for automated protein structure determination by NMR in solution. J Biomol NMR 53:341–354CrossRefGoogle Scholar
  25. Volk J, Herrmann T, Wüthrich K (2008) Automated sequence-specific protein NMR assignment using the memetic algorithm MATCH. J Biomol NMR 41:127–138CrossRefGoogle Scholar
  26. Wassenaar TA, van Dijk M, Loureiro-Ferreira N, van der Schot G, de Vries SJ, Schmitz C, van der Zwan J, Boelens R, Giachetti A, Ferella L, Rosato A, Bertini I, Herrmann T, Jonker HRA, Bagaria A, Jaravine V, Güntert P, Schwalbe H, Vranken WF, Doreleijers JF, Vriend G, Vuister GW, Franke D, Kikhney A, Svergun DI, Fogh RH, Ionides J, Laue ED, Spronk C, Jurksa S, Verlato M, Badoer S, Dal Pra S, Mazzucato M, Frizziero E, Bonvin AMJJ (2012) WeNMR: Structural biology on the grid J Grid Comput 10:743–767 doi:  10.1007/s10723-012-9246-z
  27. Williamson MP, Craven CJ (2009) Automated protein structure calculation from NMR data. J Biomol NMR 43:131–143CrossRefGoogle Scholar
  28. Zhang ZY, Porter J, Tripsianes K, Lange OF (2014) Robust and highly accurate automatic NOESY assignment and structure determination with Rosetta. J Biomol NMR 59:135–145CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Paul Guerry
    • 1
  • Viet Dung Duong
    • 1
  • Torsten Herrmann
    • 1
    Email author
  1. 1.Institut des Sciences Analytiques, Centre de RMN à très Hauts ChampsUniversité de Lyon (UMR 5280 CNRS, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1)VilleurbanneFrance

Personalised recommendations