AUTOMATED DOCKING OF ISOMALTOSE ANALOGS IN THE GLUCOAMYLASE ACTIVE-SITE

Low-energy conformers of analogues of the disaccharide isomaltose were determined with MM3(92) and were then flexibly docked into the glucoa mylase active site using AutoDock 2.1. This procedure has produced bou nd complexes of saccharides with glucoamylase comparable to those obta ined by protein crystallography. Conformational energy surfaces of thr ee methyl alpha-isomaltosides, two with a second methyl group at C-6(B ), were determined to characterize the steric limitations introduced b y that group. Their most probable conformers were used as initial stru ctures for docking. Seven sets of monodeoxy methyl alpha-isomaltoside structures were also generated based on the methyl alpha-isomaltoside conformational map and were docked to probe the contribution of indivi dual hydroxyl groups to binding. The optimized docking modes are simil ar for most analogues, and energies of intermolecular interaction per extended atom agree with the assignment of key hydroxyl groups made fr om kinetic studies. This new approach to study saccharide-protein inte ractions complements the results of protein crystallography, allowing a better understanding of the interaction of glucoamylase with its sub strates. (C) 1997 Elsevier Science Ltd.