Delineation of protein-ligand interaction modes is key for rational drug discovery. The availability of complex crystal structures is often limited by the aqueous solubility of the compounds, while lead-like compounds with micromolar affinities normally fall into the NMR intermediate exchange regime, in which severe line broadening to beyond the detection of interfacial resonances limits NMR applications. Here, we developed a new method to retrieve low-populated bound-state 1H pseudocontact shifts (PCSs) using paramagnetic relaxation dispersion (RD). We evaluated using a 1H PCS-RD approach in a BRM bromodomain lead-like inhibitor to filter molecular docking poses using multiple intermolecular structural restraints. Considering the universal presence of proton atoms in druglike compounds, our work will have wide application in structure-guided drug discovery even under an extreme condition of NMR intermediate exchange and low aqueous solubility of ligands.