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.