Transient Induced Molecular Electronic Spectroscopy (TIMES) for study of protein-ligand interactions

We present a method, Transient Induced Molecular Electronic Spectroscopy (TIMES), to detect protein-ligand interactions without any protein engineering or chemical modification. We developed a physics model for the TIMES signal and mathematically formulated the problem to attain physical insight of protein-ligand interactions without any disturbances by molecular probes, fluorescent labels, or immobilization of molecules. To demonstrate the functionality of this method, we have used the TIMES signals to find the dissociation constants for the affinity of reactions, the shear-stress dependent adsorption time of molecules on surface, and other interesting features of protein-ligand interaction in native conditions. As a unique tool, TIMES offers a simple and effective method to investigate fundamental protein chemistry and drug discoveries.