AUTOMATED DOCKING OF GLUCOSYL DISACCHARIDES IN THE GLUCOAMYLASE ACTIVE-SITE

To better understand the molecular basis of glucomylase selectivity, l ow-energy conformers of glucosyl disaccharides obtained from relaxed-r esidue conformational mapping were flexibly docked into the glucoamyla se active site using AutoDock 2.2. This procedure ensures that signifi cant conformational space is searched and can produce bound structures comparable to those obtained by protein crystallography, alpha-linked glucosyl disaccharides except alpha,alpha-trehalose dock easily into the active site while exclusively beta-linked disaccharides do not, ex plaining why only the former are glucoamylase substrates. The optimize d docking modes are similar at the nonreducing end of the different su bstrates. Individual atomic energies of intermolecular interaction all ow the definite identification of key hydroxyl groups for each substra te. This approach confirmed the versatility of the second subsite of t he glucoamylase active site in binding different substrates. (C) 1997 Wiley-Liss, Inc.