Pm. Coutinho et al., AUTOMATED DOCKING OF MONOSACCHARIDE SUBSTRATES AND ANALOGS AND METHYLALPHA-ACARVIOSINIDE IN THE GLUCOAMYLASE ACTIVE-SITE, Proteins, 27(2), 1997, pp. 235-248
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.