Solid State NMR Method for Screening Cell Membrane Protein Binding Drug Candidates
The present invention describes a method for detection of ligand-cell membrane protein binding by solid state NMR spectroscopy. The method starts by forming a lipid bilayer inside nanopores of an anodic aluminum oxide (AAO) substrate containing a membrane protein sample. The AAO substrate is treated with multiple candidate ligands having potential binding affinity for the membrane protein. Solid-state NMR analysis is performed on the treated AAO/lipid preparation so as to generate an NMR spectrum for the treated membrane protein. The possible shift in solid-state NMR spectrums between treated and untreated membrane protein is indicative of protein binding by the candidate ligand.
This new way to undertake structure-function studies of proteins provides atomic-scale structural data with minimal perturbation to the system and allows the protein to be maintained in a functionally relevant conformational state. Ideally, it possibly will allow to observe detailed molecular structure while the protein progresses through conformational states associated with normal function.