Detection of Drug Binding to a Target Protein Using EVV 2DIR Spectroscopy.

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 ∼200 detectable cross-peaks in the spectral region 1250-1750 cm/2600-3400 cm, 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.