Solid-State NMR for the Analysis of High-Affinity Ligand/Receptor Interactions

The rational development of drugs which target integral membrane proteins relies intimately on our understanding of their interactions with their binding sites. Advances in solid-state NMR methodology coupled to improved expression and purification strategies for membrane proteins now enable us to probe the structure, dynamics, and binding modes of these drugs with ever-increasing resolution. This article seeks to highlight these advances demonstrating how improvements in protein expression and purification can be coupled with recent developments in instrumentation and pulse sequences in magic-angle spinning, static, and oriented sample solid-state NMR to reveal structural and dynamic information of high-affinity drugs/ligands within their binding sites on membrane proteins. Furthermore, we will highlight some of the major experimental considerations associated with performing these studies. (C) 2009 Wiley Periodicals, Inc. Concepts Magn Reson Part A 34A: 144-172, 2009.