Enzymatic reactions are traditionally studied at the ensemble level, despite significant static and dynamic inhomogeneities.  Subtle conformational changes play a crucial role in protein functions, and these protein conformations are highly dynamic. We applied single-molecule spectroscopy to study the mechanisms and dynamics of enzymatic reactions involved with kinase and lysozyme proteins.  Enzymatic reaction turn-overs and the associated structure changes of individual protein molecules were observed simultaneously in real-time by single-molecule FRET detections.  We obtained the rates for single-molecule conformational active-site open-close fluctuation and correlated enzymatic reactions.  We have demonstrated a specific statistical analysis to reveal single-molecule FRET anti-correlated fluctuations from a high background of fluorescence correlated thermal fluctuations.  Our new approach is applicable to a wide range of single-molecule FRET measurements for protein conformational changes under enzymatic reactions.  We have also explored a combined approach, applying molecular dynamics (MD) simulation and a random-walk model based on the single-molecule experimental data.  Using this approach, we analyzed enzyme-substrate complex formation dynamics to reveal (1) multiple intermediate conformational states, (2) oscillatory conformational motions, and (3) a conformational memory effect in the chemical reaction process.