Probing and modulating enzyme conformational dynamics using single-molecule nanocircuits

Using a high-resolution single-molecule nanocircuit technique, we examined enzyme fluctuations, conformational states, and transitions in response to various ligands and non-thermal driven noise. Our results show that ligands modulate enzyme conformational dynamics, ranging from full open-to-closed transitions to minimal changes, where the enzyme shifts from an open to a slightly closed, excited state with rapid transition rates. We also investigated the effects of driven force-fields on enzyme dynamics and ligand reactivity. Our findings demonstrate that controlled external static and oscillating electric fields can synchronize and modulate protein-ligand interactions, offering a potential method for manipulating overall enzyme activity and function.