Electronic Monitoring of Ligands-Induced Conformational Dynamics of Single Lysozymes

We have investigated the dynamic interactions between lysozyme and several potential inhibitors such as peptide-based inhibitors, small-molecule inhibitors, and urea. In particular, the peptide-based inhibitor showed a weak affinity to lysozyme due to the non-covalent interactions between the C-terminus and the active site of lysozyme. Compared to the peptidoglycan substrates, the peptide inhibitor induced large conformational changes of lysozyme as well as stayed longer in the active site pockets while binding. The overall effectiveness of the peptide inhibitor was 20% when tested in the presence of both peptidoglycan substrates and inhibitors. The information gained by this research fundamentally improves our knowledge of lysozyme-inhibitor interactions, potentially paving the way to more effective, mechanism-focused drugs.