We demonstrate that electron-vibration-vibration two-dimensional infrared spectroscopy (EVV 2DIR) can be used to detect the binding of a drug to a target protein active site. The EVV 2DIR spectrum of the FGFR1 kinase target protein is found to have, similar to 200 detectable cross-peaks in the spectral region 1250-1750 cm(-1)/2600-3400 cm(-1), with additional 63 peaks caused by the addition of a drug, SU5402. Of these 63 new peaks, it is shown that only six are due to protein-drug interactions, with the other 57 being due to vibrational coupling within the drug itself. Quantum mechanical calculations employing density functional theory are used to support assignment of the six binding-dependent peaks, with one being assigned to a known interaction between the drug and a backbone carbonyl group which forms part of the binding site. None of the 57 intramolecular coupling peaks associated with the drug molecule change substantially in either intensity or frequency when the drug binds to the target protein. This strongly suggests that the structure of the drug in the target binding site is essentially identical to that when it is not bound.