NMR Spectroscopy Tools for Structure‐Aided Drug Design

Abstract

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.