This is a competitive renewal application for a grant that supports the Biotechnology Resource for NMR Molecular Imaging of Proteins at the University of California, San Diego. The BTRC develops and applies NMR spectroscopy for the study of proteins in biological supermolecular structures, such as virus particles and membranes. Successful applications of nuclear magnetic resonance (NMR) spectroscopy to proteins have been largely limited to the same class of soluble, globular proteins that are amenable to X-ray crystallography. However, methods that work well with globular proteins typically work poorly with membrane proteins in their native crystalline phospholipid bilayer environment. It is this technology gap that we seek to fill. The BTRC is highly focused on advancing the technology for high-resolution solid-state NMR spectroscopy so that it can be used in laboratories throughout the World to determine the structure of membrane proteins under near-native conditions. It is this unique technology that we will make available to the Nation's biomedical research community through our Collaborative (CP) and Service (SP) research projects. Membrane proteins are important targets for structural studies because they represent about one-third of the proteins expressed from the genomes of all organisms and have many unique roles, including as drug receptors where they have their greatest biomedical roles. Primary targets for the research at the BTRC include G-protein coupled receptors (GPCRs), which are the largest class of membrane proteins and of drug receptors. Information about their structures will help guide the development of new drugs for a wide range of diseases, ranging from cancer to mental illness.
The technology developed at the BTRC will accelerate the development of drugs against a wide range of diseases. The information gained in the studies carried out with this technology will disclose the details of how drugs bind to their molecular partners, which are the actual players the affect diseases. This information will help in the discovery of new drugs.
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