Presentation: 2025 ND EPSCoR Annual conference 

October 21, 2025, NDSU Memorial Union, Fargo, North Dakota

Regulation of Enzyme Dynamics by Ligand Binding and Stochastic Fluctuations

This research elucidates the mechanisms of ligand-induced conformational dynamics and the role of noise in enzyme function. Using a high-resolution, single-molecule nanocircuit technique, we directly observed the real-time structural dynamics of individual lysozyme molecules. Our results reveal that the enzyme's conformational pathway is strictly controlled by the identity of the bound ligand. When interacting with its natural substrate, peptidoglycan, lysozyme undergoes a complete catalytic cycle, transitioning through open, intermediate, and catalytically active closed states. In contrast, binding to substrate analogs or inhibitors traps the enzyme in an incomplete cycle, restricting it to rapid, small-scale fluctuations between an open and a non-productive, partially closed state. Furthermore, we find that non-thermal noise actively modulates the kinetics of these transitions. Contrary to being a purely disruptive force, these environmental fluctuations can synchronize conformational changes, suggesting a physical mechanism for tuning an enzyme's catalytic efficiency and substrate specificity. This work was supported by NSF (CBET-2317111).