By combining experiments and simulations we developed a unique technique to detect protein-ligand binding, based on the Transient Induced Molecular Electronic Spectroscopy (TIMES). Our approach of TIMES is in label-free and restriction-free condition, which reveals true physiological feature of the reaction and will be an important application in protein detection and drug discovery. Using TIMES, we tested protein with different concentration and different flow rate in microfluidic channel, and obtained the information about how the protein molecules reach and leave the gold electrode. The attractive protein-electrode force and repulsive shear force in microfluid channel drive the protein motion, meanwhile electric signal is generated. When protein-ligand binding happens and the complex forms, electrostatic force between molecule and electrode changes, thus the electric signal changes due to the dwelling time of molecule on the electrode surface change. With the induced electric signal on the electrode upon proteins dwelling on the surface, we systematically investigated the effects of protein and ligand concentration and hydraulic shear stress on protein-ligand binding and proteins’ kinetic transport at the water-surface interface inside a microfluidic channel. Our full-atom molecule dynamics simulation demonstrated the image charges on polarized gold surface due to the dipole moment of a protein molecule. The interactions between protein and gold surface’s image charges as well as the surface hydrophobicity, protein-surface thio-interactions and protein dehydration were also examined at the atomistic scale. <br/>

Development of transient induced molecular electronic spectroscopy (TIMES) for protein-ligand interactions

251st National Meeting (2016)

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