NMR spectroscopy and protein structure determination: applications to drug discovery and development

Curr Pharm Biotechnol. 2005 Apr;6(2):105-20. doi: 10.2174/1389201053642367.

Abstract

Recent technological advances in NMR methods and instrumentation are having a significant impact in structural biology. These innovations are also impacting pharmaceutical biotechnology as it is now possible to use NMR spectroscopy to rapidly characterize a growing number of prospective protein drugs and protein drug targets. This review provides a general summary of how solution-state NMR can be used to determine protein structures. It also focuses on exploring how advances in solution state NMR are changing the way in which protein structures can be determined and protein-ligand interactions can be characterized. Recent innovations in protein sample preparation, in instrumentation and data collection, in spectral assignment and in structure generation are highlighted. The impact of solution-state NMR on pharmaceutical biotechnology is also discussed, with a special emphasis on describing how NMR has been used to study a number of pharmaceutically important proteins and how NMR is currently being used to rapidly screen and to map the binding sites of small molecules to a range of protein targets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Computer Simulation
  • Drug Design*
  • Models, Molecular*
  • Nuclear Magnetic Resonance, Biomolecular / instrumentation*
  • Nuclear Magnetic Resonance, Biomolecular / methods*
  • Protein Conformation
  • Protein Interaction Mapping / instrumentation
  • Protein Interaction Mapping / methods
  • Proteins / analysis*
  • Proteins / chemistry*
  • Sequence Analysis, Protein / instrumentation*
  • Sequence Analysis, Protein / methods*
  • Sequence Analysis, Protein / trends

Substances

  • Proteins