Molecular dynamics simulations on the complexes of glucoamylase II (471) from Asgergillus awamori var. X100 with 1-deoxynojirimycin and lentiginosine

Molecular dynamics (MD) simulations on the complexes of glucoamylase II (471) from Aspergillus awamori var. X100 with two powerful inhibitors, 1-deoxynojirimycin and (+)-lentiginosine, have been performed, in order to build a model for these complexes in solution and to clarify the structure-activity relationship. MD calculations were carried out for 105 ps, over a 15 Angstrom sphere centered on the inhibitors. A 8 Angstrom residue-based cut-off was used, and the calculations were performed with explicit inclusion of solvent molecules. The MD structure of the complex 1-deoxynojirimycin-glucoamylase shows only minor deviations from the available X-ray structure. The MD structure of the complex of (+)-lentiginosine-glucoamylase, obtained by docking the inhibitor into the active site, suggests us a suitable orientation for the molecule into the enzyme cavity, which can rationalize the high inhibition activity found for (+)-lentiginosine towards amyloglucosidase from A. niger