Modeling of deoxy- and dideoxyaldohexopyranosyl ring puckering with MM3(92).

Extensive variations of the ring structures of three deoxyaldohexopyranoses, L-fucose, D-quinovose, and L-rhamnose, and four dideoxyaldohexopyranoses, D-digitoxose, abequose, paratose, and tyvelose, were studied by energy minimization with the molecular mechanics algorithm MM3(92). Chair conformers, 4C(1) in D-quinovose and the equivalent 1C(4) in L-fucose and L-rhamnose, overwhelmingly dominate in the three deoxyhexoses; in the D-dideoxyhexoses, 4C(1) is again dominant, but with increased amounts of 1C(4) forms in the alpha anomers of the three 3,6-dideoxyhexoses, abequose, paratose, and tyvelose and in both alpha and beta anomers of the 2,6-dideoxyhexose D-digitoxose. In general, modeled proton-proton coupling constants agreed well with experimental values. Computed anomeric ratios strongly favor the beta configuration except for D-digitoxose, which is almost equally divided between alpha and beta configurations, and L-rhamnose, where the beta configuration is somewhat favored. MM3(92) appears to overstate the prevalence of the equatorial beta anomer in all three deoxyhexoses, as earlier found with fully oxygenated aldohexopyranoses.

Automated docking of alpha-(1-->4)- and alpha-(1-->6)-linked glucosyl trisaccharides and maltopentaose into the soybean beta-amylase active site.

The Lamarckian genetic algorithm of AutoDock 3.0 was used to dock alpha-maltotriose, methyl alpha-panoside, methyl alpha-isopanoside, methyl alpha-isomaltotrioside, methyl alpha-(6(1)-alpha-glucopyranosyl)-maltoside, and alpha-maltopentaose into the closed and, except for alpha-maltopentaose, into the open conformation of the soybean beta-amylase active site. In the closed conformation, the hinged flap at the mouth of the active site closes over the substrate. The nonreducing end of alpha-maltotriose docks preferentially to subsites -2 or +1, the latter yielding nonproductive binding. Some ligands dock into less optimal conformations with the nonreducing end at subsite -1. The reducing-end glucosyl residue of nonproductively-bound alpha-maltotriose is close to residue Gln194, which likely contributes to binding to subsite +3. In the open conformation, the substrate hydrogen-bonds with several residues of the open flap. When the flap closes, the substrate productively docks if the nonreducing end is near subsites -2 or -1. Trisaccharides with alpha-(1-->6) bonds do not successfully dock except for methyl alpha-isopanoside, whose first and second glucosyl rings dock exceptionally well into subsites -2 and -1. The alpha-(1-->6) bond between the second and third glucosyl units causes the latter to be improperly positioned into subsite +1; the fact that isopanose is not a substrate of beta-amylase indicates that binding to this subsite is critical for hydrolysis.