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Automated docking of maltose, 2‐deoxymaltose, and maltotetraose into the soybean β‐amylase active site
Author(s) -
Laederach Alain,
Dowd Michael K.,
Coutinho Pedro M.,
Reilly Peter J.
Publication year - 1999
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(19991101)37:2<166::aid-prot3>3.0.co;2-e
Subject(s) - chemistry , docking (animal) , maltose , stereochemistry , conformational isomerism , active site , autodock , crystallography , molecule , enzyme , biochemistry , organic chemistry , medicine , nursing , in silico , gene
In this study, products and substrates were docked into the active site of β‐amylase using the simulated annealing algorithm AutoDock. Lowest‐energy conformers reproduced known crystallographic atom positions within 0.4 to 0.8 Å rmsd. Docking studies were carried out with both open and closed configurations of the β‐amylase mobile flap, a loop comprising residues 96 to 103. Ligands with two rings docked within the cleft near the active site when the flap was open, but those with four rings did not. The flap must be closed for α‐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 therefore it plays a essential role in catalysis. The gain in total binding energy upon closing of the flap for α‐maltose docked to subsites −2,−1 and +1,+2 is about 22 kcal/mol, indicating more favorable interactions are possible with the flap closed. Larger intermolecular interaction energies are observed for two α‐maltose molecules docked to subsites −2, −1 and +1,+2 than for one α‐maltotetraose molecule docked from subsites −2 to +2, suggesting that it is only upon cleavage of the α‐1,4 linkage that optimal closed‐flap binding can occur with the crytallographically determined enzyme structure. Proteins 1999;37:166–175. ©1999 Wiley‐Liss, Inc.