Overview of Probing Protein‐Ligand Interactions Using NMR. (3rd August 2015)

• Record Type: Journal Article
• Authors: Aguirre, Clémentine; Cala, Olivier; Krimm, Isabelle
• Editors: Coligan, John E.; Dunn, Ben M.; Speicher, David W.; Wingfield, Paul T.
• Is Part Of: Current protocols in protein science. Volume 81(2015)
• Page Start: 17.18.1
• Page End: 17.18.24
• Publication Date: 2015-08-03
• Subjects: NMR -- ligand -- NOE -- INPHARMA -- WaterLOGSY -- chemical shift perturbations -- 3D structure; Proteins -- Laboratory manuals; Proteins; Clinical Laboratory Techniques; Genetic Techniques; Immunologic Techniques; Proteins; Laboratory manuals; 572.6028
• DOI: 10.1002/0471140864.ps1718s81
• Languages: English
• ISSNs: 1934-3655

Abstract

Abstract: Nuclear magnetic resonance (NMR) is a powerful technique for the study and characterization of protein‐ligand interactions. In this unit we review both experiments where the NMR spectrum of the protein is observed (protein‐observed NMR experiments) and those where the NMR spectra of the ligand is observed (ligand‐observed NMR experiments) for the identification of binding partners, the measurement of protein‐ligand affinity, the design of molecules that are active against biological targets such as proteins, and the assessment of the binding modes of the ligands. Ligand‐observed methods discussed in this unit are Nuclear Overhauser Effect (NOE)—based approaches, with well‐known experiments such as the Saturation Transfer Difference, Water‐Ligand Observed via Gradient Spectroscopy (WaterLOGSY), and transferred—Nuclear Overhauser Effect Spectroscopy (tr‐NOESY) experiments, and also the INPHARMA experiment. Regarding protein‐observed experiments, this unit focuses on the use of chemical shift perturbations observed in protein‐NMR spectra upon ligand binding. Also discussed is how these chemical shift perturbations can be used for the analysis of protein‐ligand complexes, including fast structure determination when combined with docking. © 2015 by John Wiley & Sons, Inc.