Informace o publikaci
Reaction mechanism study of retaining glycosyltransferase using QM/MM metadynamics and string method
| Autoři | |
|---|---|
| Rok publikování | 2015 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Glycosyltransferases are enzymes that catalyze the formation of glycosidic linkages. They are responsible for synthesis of complex glycan structures of various biological functions and thus impact huge range of biological processes. In our work we study the reaction mechanism of metal dependent retaining glycosyltransferase polypeptide UDP-GalNAc transferase 2 (ppGalNAcT2) that catalyzes the first step in mucin type O-glycosylation. It transfers GalNAc moiety from UDP-GalNAc to the hydroxyl group of either threonine or serine residue on the target protein. We use QM/MM Car–Parrinello molecular dynamics simulations, where the key region of the enzymatic reaction is treated at a DFT level of theory, while the rest of the system is described by computationally less demanding force field. The free energy surface of the reaction is roughly explored by two-dimensional metadynamics simulation. The string method is subsequently used to obtain optimized minimum free energy path between reactants and products. Combining these two methods we can get relatively rough overview of the free energy landscape from metadynamics and a free energy profile of the optimized minimum free energy path from string method. |