Modulation of Enzyme Conformational States by Ligands and Noise

Using a high-resolution single-molecule nanocircuit technique, we studied enzyme fluctuations, conformational states, and transitions in response to various ligands. Our findings revealed that specific ligands modulate enzyme conformational dynamics. For instance, lysozyme interacting with peptidoglycan substrates exhibited dynamic shifts between open, intermediate, and fully closed hydrolysis-ready states, with occasional interruptions. In contrast, when bound to substrate analogs and indole derivative inhibitors, lysozyme displayed minimal conformational changes, transitioning only from an open to a slightly closed, excited state with rapid transition rates. We also investigated the effect of non-thermal noise on these transitions, finding that it could synchronize and modulate conformational shifts, influencing enzyme specificity and catalytic activity. This work was supported by NSF (CBET-2317111).