Drug discovery processes require the determination of the protein binding site structure, which can be achieved via nuclear magnetic resonance (NMR) spectroscopy. While traditional NMR spectroscopy suffers from low sensitivity, NMR signals can be significantly enhanced through hyperpolarization of nuclear spins. Here, folic acid is hyperpolarized by dissolution dynamic nuclear polarization (D-DNP). Polarization transfer to dihydrofolate reductase is compared to signal evolution predicted for docking-derived structures. The results demonstrate that a scoring function derived from the experimental data improves the ranking of structures. With data from six methyl groups, Spearman's correlation coefficient of the experimental scoring function to the root-mean-square deviation from a reference structure is 0.88 for five individually addressed ligand protons and 0.59 for the entire ligand, while the same correlation coefficient of the energy calculated from docking alone is 0.49. D-DNP NMR-derived ranking, therefore, is capable of determining the ligand structure with a small number of individually addressed source spins.