Publication details
Reaction mechanism of ppGalNAcT2: QM/MM Metadynamics and String Method
| Authors | |
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| Year of publication | 2015 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Polypeptide UDP-GalNAc transferase (ppGalNAcT2) is a metal dependent retaining glycosyltransferase of GT-A fold 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 hybrid QM/MM Car–Parrinello molecular dynamics simulations in order to study the reaction mechanism. In this approach the key region where the enzymatic reaction is occurring 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 metadynamics methodology and the minimum free energy path between reactants and products is optimized using string method. Combining these two methods we obtain relatively rough overview of the free energy landscape and an accurate estimation of the free energy barrier for the glycosyltransferase reaction. |