NMR spectroscopy tools for structure-aided drug design.
Biomolecular NMR spectroscopy has expanded dramatically in recent years and is now a powerful tool for the study of structure, dynamics, and interactions of biomolecules. Previous limitations with respect to molecular size are no longer a primary barrier, and systems as large as 900 kDa were recently studied. NMR spectroscopy is already well-established as an efficient method for ligand screening. A number of recently developed techniques show promise as aids in structure-based drug design, for example, in the rapid determination of global protein folds, the structural characterization of ligand-protein complexes, and the derivation of thermodynamic parameters. An advantage of the method is that all these interactions can be studied in solution--time-consuming crystallization is not necessary. This Review focuses on recent developments in NMR spectroscopy and how they might be of value in removing some of the current "bottlenecks" in structure-based drug discovery.
Homans
Steve W
SW
School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK. s.w.homans@leeds.ac.uk
D000818:Animals; D015195:Drug Design; D006801:Humans; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
D008024:Ligands; D011506:Proteins