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Macromolecular structure determination typically involves multiple different NMR experiments to interrogate the different facets of the covalent adduct, but 2D NMR techniques that detect the scalar (through multiple bonds) correlation of protein atoms to ligand atoms (e.g., pulse programs based on (HSQC-)TOCSY, HMBC, or 2D-INADEQUATE) ultimately provide the most conclusive NMR-based evidence of a covalent protein–drug adduct because these correlations are exclusive to covalent adducts
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