Automated docking of isomaltose analogues 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 glucoamylase active site using AutoDock 2.1. This procedure has produced bound complexes of saccharides with glucoamylase comparable to those obtained by protein crystallography. Conformational energy surfaces of three methyl alpha-isomaltosides, two with a second methyl group at C-6(B), were determined to characterize the steric limitations introduced by that group. Their most probable conformers were used as initial structures 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 individual hydroxyl groups to binding. The optimized docking modes are similar for most analogues, and energies of intermolecular interaction per extended atom agree with the assignment of key hydroxyl groups made from kinetic studies. This new approach to study saccharide-protein interactions complements the results of protein crystallography, allowing a better understanding of the interaction of glucoamylase with its substrates. (C) 1997 Elsevier Science Ltd.