Higher energy states of protein and nucleic acids critically determine their biological functions. They exhibit large single-molecule heterogeneity in structure and dynamics. We are interested in seeing how protein-DNA/RNA complex and assembly emerge from interactions that are easily perturbed by thermal fluctuation and external environments. We seek to resolve the conformational dynamics of these processes with combined methods (liquid phase electron microscopy and fluorescence methods) to understand error production/correction mechanisms that are relevant to public health, precision medicine, and disease diagnosis.