Determination of protein-ligand binding modes using fast multi-dimensional NMR with hyperpolarization.

ABSTRACT: Elucidation of small molecule-protein interactions provides essential information for understanding biological processes such as cellular signaling, as well as for rational drug development. Here, multi-dimensional NMR with sensitivity enhancement by dissolution dynamic nuclear polarization (D-DNP) is shown to allow the determination of the binding epitope of folic acid when complexed with the target dihydrofolate reductase. Protein signals are selectively enhanced by polarization transfer from the hyperpolarized ligand. A pseudo three-dimensional data acquisition with ligand-side Hadamard encoding results in protein-side [¹³C, ¹H] chemical shift correlations that contain intermolecular nuclear Overhauser effect (NOE) information. A scoring function based on this data

SUBMITTER: Wang Y 

PROVIDER: S-EPMC7441707 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature