Carbohydrate-active enzymes, such as glycoside hydrolases (GHs) and glycosyltransferases (GTs), constitute the main machinery for the degradation and synthesis of glycosidic bonds in nature. They have a myriad of industrial and biotechnological applications, ranging from biofuel production to drug design. In recent years, we have investigated catalytic mechanisms in these enzymes using state-of-art simulation techniques such as ab initio quantum mechanics/molecular mechanics (QM/MM) and metadynamics , providing a microscopic view of enzyme action. The simulations reveal the nature of the reaction transition states and the conformational itineraries of substrates in GHs [2-4], often encoded in the conformational energy landscape of isolated sugars , and complex GT catalytic pathways . In this talk I will highlight some of the work that we have done in last years, in close collaboration with research groups of chemical and structural biology. Sugar conformational dynamics and the formation of short-lived species on the pathway to glycosidic bond formation will be discussed.
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