AUTOMATED DOCKING OF MONOSACCHARIDE SUBSTRATES AND ANALOGS AND METHYLALPHA-ACARVIOSINIDE IN THE GLUCOAMYLASE ACTIVE-SITE

Glucoamylase is an important industrial glucohydrolase with a large sp ecificity range, To investigate its interaction with the monosaccharid es D-glucose, D-mannose, and D-galactose and with the substrate analog ues 1-deoxynojirimycin, D-glucono-1,5-lactone, and methyl alpha-acarvi osinide, MM3(92)-optimized structures were docked into its active site using AutoDock 2.1. The results were compared to structures of glucoa mylase complexes obtained by protein crystallography, Charged forms of some substrate analogues were also docked to assess the degree of pro tonation possessed by glucoamylase inhibitors. Many forms of methyl al pha-acarviosinide were conformationally mapped by using MM3(92), chara cterizing the conformational pH dependence found for the acarbose fami ly of glucosidase inhibitors. Their significant conformers, representi ng the most common states of the inhibitor, were used as initial struc tures for docking, This constitutes a new approach for the exploration of binding modes of carbohydrate chains, Docking results differ sligh tly from x-ray crystallographic data, the difference being of the orde r of the crystallographic error. The estimated energetic interactions, even though agreeing in some cases with experimental binding kinetics , are only qualitative due to the large approximations made by AutoDoc k force field. (C) 1997 Wiley-Liss, Inc.