Journal of Biomolecular NMR

, Volume 42, Issue 2, pp 111–127 | Cite as

Direct methods and residue type specific isotope labeling in NMR structure determination and model-driven sequential assignment

  • Andreas Schedlbauer
  • Renate Auer
  • Karin Ledolter
  • Martin Tollinger
  • Karin Kloiber
  • Roman Lichtenecker
  • Simon Ruedisser
  • Ulrich Hommel
  • Walther Schmid
  • Robert Konrat
  • Georg KontaxisEmail author


Direct methods in NMR based structure determination start from an unassigned ensemble of unconnected gaseous hydrogen atoms. Under favorable conditions they can produce low resolution structures of proteins. Usually a prohibitively large number of NOEs is required, to solve a protein structure ab-initio, but even with a much smaller set of distance restraints low resolution models can be obtained which resemble a protein fold. One problem is that at such low resolution and in the absence of a force field it is impossible to distinguish the correct protein fold from its mirror image. In a hybrid approach these ambiguous models have the potential to aid in the process of sequential backbone chemical shift assignment when 13Cβ and 13C′ shifts are not available for sensitivity reasons. Regardless of the overall fold they enhance the information content of the NOE spectra. These, combined with residue specific labeling and minimal triple-resonance data using 13Cα connectivity can provide almost complete sequential assignment. Strategies for residue type specific labeling with customized isotope labeling patterns are of great advantage in this context. Furthermore, this approach is to some extent error-tolerant with respect to data incompleteness, limited precision of the peak picking, and structural errors caused by misassignment of NOEs.


Direct NMR methods Proton density clouds NMR sequential assignment Residue type specific isotope labeling 

Supplementary material

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Andreas Schedlbauer
    • 1
  • Renate Auer
    • 1
  • Karin Ledolter
    • 1
  • Martin Tollinger
    • 1
  • Karin Kloiber
    • 1
  • Roman Lichtenecker
    • 2
  • Simon Ruedisser
    • 3
  • Ulrich Hommel
    • 3
  • Walther Schmid
    • 2
  • Robert Konrat
    • 1
  • Georg Kontaxis
    • 1
    Email author
  1. 1.Institute of Biomolecular Structural Chemistry, Max F. Perutz LaboratoriesUniversity of ViennaViennaAustria
  2. 2.Institute of Organic ChemistryUniversity of ViennaViennaAustria
  3. 3.Novartis Institutes for BioMedical ResearchBaselSwitzerland

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