This invention relates broadly to the structure of macromolecules and more specifically to nuclear magnetic resonance (NMR) methods for preferentially observing exposed positions of a macromolecule.
The three-dimensional structure of macromolecules such as proteins can provide insight into their function in normal and diseased cells. For example, when certain compounds or “ligands” bind to a protein, the 3-D structure of the protein can help identify the ligand's binding sites on the protein. Atomic-resolution structures can allow researchers to understand the interaction between ligands and macromolecules and to design and select new ligands that may serve as therapeutic drugs.
Nuclear magnetic resonance (NMR) spectroscopy has determined the structure of many proteins at atomic resolution. Nevertheless, current NMR methods for protein structure determination are extremely time-consuming because they require painstaking deduction of the positions of thousands of individual atoms. As attention focuses on larger and more complex proteins and the number of atoms increases, the data generated by NMR methods can become overwhelming, making it virtually impossible to determine the structure of the protein.
Thus, there is a need for methods that can provide information about large macromolecular structures in a way that is useful for understanding ligand binding. The present invention satisfies this need and provides related advantages as well.