Protein NMR pp 111-132 | Cite as

Rapid Prediction of Multi-dimensional NMR Data Sets Using FANDAS

  • Siddarth Narasimhan
  • Deni Mance
  • Cecilia Pinto
  • Markus Weingarth
  • Alexandre M. J. J. Bonvin
  • Marc BaldusEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1688)


Solid-state NMR (ssNMR) can provide structural information at the most detailed level and, at the same time, is applicable in highly heterogeneous and complex molecular environments. In the last few years, ssNMR has made significant progress in uncovering structure and dynamics of proteins in their native cellular environments [1–4]. Additionally, ssNMR has proven to be useful in studying large biomolecular complexes as well as membrane proteins at the atomic level [5]. In such studies, innovative labeling schemes have become a powerful approach to tackle spectral crowding. In fact, selecting the appropriate isotope-labeling schemes and a careful choice of the ssNMR experiments to be conducted are critical for applications of ssNMR in complex biomolecular systems. Previously, we have introduced a software tool called FANDAS (Fast Analysis of multidimensional NMR DAta Sets) that supports such investigations from the early stages of sample preparation to the final data analysis [6]. Here, we present a new version of FANDAS, called FANDAS 2.0, with improved user interface and extended labeling scheme options allowing the user to rapidly predict and analyze ssNMR data sets for a given protein-based application. It provides flexible options for advanced users to customize the program for tailored applications. In addition, the list of ssNMR experiments that can be predicted now includes proton (1H) detected pulse sequences. FANDAS 2.0, written in Python, is freely available through a user-friendly web interface at

Key words

Biomolecular NMR Labeling schemes Spectral prediction Spectral analysis and proton detection 



This work was funded in part by the Netherlands Organization for Scientific Research (NWO) (grants 700.26.121 and 700.10.443 to M.B.). The development of the web portal was supported by a European H2020 e-Infrastructure grant West-Life (grant no. 675858 to A.B.). The authors would like to thank Panagiotis Koukos of the Computational Structural Biology Group for his humble assistance in hosting the webserver.


  1. 1.
    Renault M, Pawsey S, Bos MP, Koers EJ, Nand D, Tommassen-van Boxtel R, Rosay M, Tommassen J, Maas WE, Baldus M (2012) Solid-state NMR spectroscopy on cellular preparations enhanced by dynamic nuclear polarization. Angew Chem Int Ed Engl 51(12):2998–3001. CrossRefPubMedGoogle Scholar
  2. 2.
    Renault M, Tommassen-van Boxtel R, Bos MP, Post JA, Tommassen J, Baldus M (2012) Cellular solid-state nuclear magnetic resonance spectroscopy. Proc Natl Acad Sci USA 109(13):4863–4868 10.1073/pnas.1116478109 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Kaplan M, Cukkemane A, van Zundert GC, Narasimhan S, Daniels M, Mance D, Waksman G, Bonvin AM, Fronzes R, Folkers GE, Baldus M (2015) Probing a cell-embedded megadalton protein complex by DNP-supported solid-state NMR. Nat Methods 12(7):649–652. CrossRefPubMedGoogle Scholar
  4. 4.
    Kaplan M, Narasimhan S, de Heus C, Mance D, van Doorn S, Houben K, Popov-Celeketic D, Damman R, Katrukha EA, Jain P, Geerts WJ, Heck AJ, Folkers GE, Kapitein LC, Lemeer S, van Bergen En Henegouwen PM, Baldus M (2016) EGFR dynamics change during activation in native membranes as revealed by NMR. Cell 167(5):1241–1251. e1211.
  5. 5.
    Kaplan M, Pinto C, Houben K, Baldus M (2016) Nuclear magnetic resonance (NMR) applied to membrane-protein complexes. Q Rev Biophys 49:e15. CrossRefPubMedGoogle Scholar
  6. 6.
    Gradmann S, Ader C, Heinrich I, Nand D, Dittmann M, Cukkemane A, van Dijk M, Bonvin AM, Engelhard M, Baldus M (2012) Rapid prediction of multi-dimensional NMR data sets. J Biomol NMR 54(4):377–387. CrossRefPubMedGoogle Scholar
  7. 7.
    Sinnige T, Weingarth M, Renault M, Baker L, Tommassen J, Baldus M (2014) Solid-state NMR studies of full-length BamA in lipid bilayers suggest limited overall POTRA mobility. J Mol Biol 426(9):2009–2021. CrossRefPubMedGoogle Scholar
  8. 8.
    Sinnige T, Houben K, Pritisanac I, Renault M, Boelens R, Baldus M (2015) Insight into the conformational stability of membrane-embedded BamA using a combined solution and solid-state NMR approach. J Biomol NMR 61(3–4):321–332. CrossRefPubMedGoogle Scholar
  9. 9.
    Baker LA, Daniels M, van der Cruijsen EAW, Folkers GE, Baldus M (2015) Efficient cellular solid-state NMR of membrane proteins by targeted protein labeling. J Biomol NMR 62(2):199–208. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Renault M, Cukkemane A, Baldus M (2010) Solid-state NMR spectroscopy on complex biomolecules. Angew Chem Int Ed Engl 49(45):8346–8357. CrossRefPubMedGoogle Scholar
  11. 11.
    Pauli J, Baldus M, van Rossum B, de Groot H, Oschkinat H (2001) Backbone and side-chain 13C and 15N signal assignments of the alpha-spectrin SH3 domain by magic angle spinning solid-state NMR at 17.6 Tesla. Chembiochem 2(4):272–281CrossRefPubMedGoogle Scholar
  12. 12.
    Sinnige T, Daniels M, Baldus M, Weingarth M (2014) Proton clouds to measure long-range contacts between nonexchangeable side chain protons in solid-state NMR. J Am Chem Soc 136(12):4452–4455. CrossRefPubMedGoogle Scholar
  13. 13.
    Mance D, Sinnige T, Kaplan M, Narasimhan S, Daniels M, Houben K, Baldus M, Weingarth M (2015) An Efficient labelling approach to harness backbone and side-chain protons in 1H-detected solid-state NMR spectroscopy. Angew Chem Int Ed Engl 54(52):15799–15803 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Goddard TD, Kneller DG SPARKY 3. University of California, San FranciscoGoogle Scholar
  15. 15.
    Wang Y, Jardetzky O (2002) Probability-based protein secondary structure identification using combined NMR chemical-shift data. Protein Sci 11(4):852–861. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Joosten RP, te Beek TA, Krieger E, Hekkelman ML, Hooft RW, Schneider R, Sander C, Vriend G (2011) A series of PDB related databases for everyday needs. Nucleic Acids Res 39(Database issue):D411–D419. CrossRefPubMedGoogle Scholar
  17. 17.
    Frishman D, Argos P (1995) Knowledge-based protein secondary structure assignment. Proteins 23(4):566–579. CrossRefPubMedGoogle Scholar
  18. 18.
    Drozdetskiy A, Cole C, Procter J, Barton GJ (2015) JPred4: a protein secondary structure prediction server. Nucleic Acids Res 43(W1):W389–W394. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Jones DT (1999) Protein secondary structure prediction based on position-specific scoring matrices. J Mol Biol 292(2):195–202. CrossRefPubMedGoogle Scholar
  20. 20.
    Han B, Liu Y, Ginzinger SW, Wishart DS (2011) SHIFTX2: significantly improved protein chemical shift prediction. J Biomol NMR 50(1):43–57. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    LeMaster DM, Kushlan DM (1996) Dynamical mapping of E. coli thioredoxin via 13C NMR relaxation analysis. J Am Chem Soc 118(39):9255–9264 doi: CrossRefGoogle Scholar
  22. 22.
    Hong M, Jakes K (1999) Selective and extensive 13C labeling of a membrane protein for solid-state NMR investigations. J Biomol NMR 14(1):71–74CrossRefPubMedGoogle Scholar
  23. 23.
    Castellani F, van Rossum B, Diehl A, Schubert M, Rehbein K, Oschkinat H (2002) Structure of a protein determined by solid-state magic-angle-spinning NMR spectroscopy. Nature 420(6911):98–102. CrossRefPubMedGoogle Scholar
  24. 24.
    Nand D, Cukkemane A, Becker S, Baldus M (2012) Fractional deuteration applied to biomolecular solid-state NMR spectroscopy. J Biomol NMR 52(2):91–101. CrossRefPubMedGoogle Scholar
  25. 25.
    Weingarth M, Demco DE, Bodenhausen G, Tekely P (2009) Improved magnetization transfer in solid-state NMR with fast magic angle spinning. Chem Phys Lett 469(4–6):342–348. CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  • Siddarth Narasimhan
    • 1
  • Deni Mance
    • 1
  • Cecilia Pinto
    • 1
  • Markus Weingarth
    • 1
  • Alexandre M. J. J. Bonvin
    • 2
  • Marc Baldus
    • 1
    Email author
  1. 1.NMR SpectroscopyBijvoet Center for Biomolecular Research, Utrecht UniversityUtrechtThe Netherlands
  2. 2.Computational Structural BiologyBijvoet Center for Biomolecular Research, Utrecht UniversityUtrechtThe Netherlands

Personalised recommendations