Automated docking of maltose, 2-deoxymaltose, and maltotetraose into the soybean beta-amylase active site

In this study, products and substrates were docked into the active site of beta-amylase using the simulated annealing algorithm AutoDock, Lowest-energ y conformers reproduced known crystallographic atom positions within 0.4 to 0.8 Angstrom rmsd. Docking studies were carried out with both open and clo sed configurations of the beta-amylase mobile flap, a loop comprising resid ues 96 to 103, Ligands with two rings docked within the cleft near the acti ve site when the flap was open, but those with four rings did not. The flap must be closed for alpha-maltotetraose to adopt a conformation allowing it to dock near the crystallographically determined subsites, The closed flap is necessary for productive but not for nonproductive binding, and therefo re it plays a essential role in catalysis, The gain in total binding energy upon closing of the flap for alpha-maltose docked to subsites -2, -1 and 1, +2 is about 22 kcal/mol, indicating more favorable interactions are poss ible with the flap closed, Larger intermolecular interaction energies are o bserved for two alpha-maltose molecules docked to subsites -2, -1 and +1, 2 than for one alpha-maltotetraose molecule docked from subsites -2 to +2, suggesting: that it is only upon cleavage of the alpha-1,4 linkage that opt imal closed-flap binding can occur with the crytallographically determined enzyme structure. Proteins 1999;37:166-175, (C) 1999 WiIey-Liss, Inc.