New methods have been developed which enhance the sensitivity of protein NMR by transferring magnetization from the H2O solvent to the protein. Pulsed field gradients and selective pulses are used to ensure that the water magnetization remains close to its equilibrium value during the entire experiment. Cross relaxation and exchange of labile protein protons with solvent then result in increased protein signal intensity. The enhancement ranges from 10-50% for most experiments that are conducted in H2O solution, to a three-fold enhancement when studying the interaction between solvent and protein. This new methodology was used to prove that the HIV protease inhibitor DMP-323 indeed displaces the conserved water molecule observed in other complexes between inhibitors and the protease.