Flow-Through Lipid Nanotube Arrays for Structure-Function Studies of Membrane Proteins by Solid State NMR
The proposed invention is a novel solid state NMR based technology that takes advantage of a recent finding that uses Anodic Aluminum Oxide (AAO) nano-porous filters to uniformly align membrane proteins in the NMR spectrometer. The technology is similar to SAR by NMR but is applicable to Membrane Proteins, a class of proteins that accounts for more than 60% of all current drug targets.
- This novel NMR approach can be applied to all membrane proteins with well-aligned membrane protein samples in bicelles or AAO filters
- This approach can be used for drug development for all infectious diseases, including Mycobacterium Tuberculosis
- This NMR technique can be used for target-based screening for membrane proteins
- Allow pharmaceutical research to identify which protein targets may respond to drugs and which targets are relevant to disease
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.