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 studie