|Coutinho, P - IOWA STATE UNIVERSITY|
|Reilly, P - IOWA STATE UNIVERSITY|
Submitted to: Carbohydrate Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 14, 1996
Publication Date: N/A
Interpretive Summary: A detailed understanding of the binding of carbohydrates with the enzyme glucoamylase is needed in order to direct future genetic modification research focused on producing enzymes with altered properties. In this report, the shapes of several compounds were studied by molecular mechanics modeling. The most likely molecular shapes were used as starting structures to study the binding of these compounds to glucoamylase. The binding studies were carried out using specialized programs. The resulting bound conformations were similar for most of the compounds studied, and the interactions between the carbohydrate and the enzyme were strongest for parts of the molecule that are known experimentally to be important for binding. This new approach for studying carbohydrate-protein interactions complements the results of protein crystallography.
Technical Abstract: Analogues of isomaltose were subjected to relaxed-residue conformational analysis with MM3(92) and then flexibly docked into the glucoamylase active site using AutoDock 2.1. Three methyl a-isomaltosides, two with an extra methyl group at C-6B, were conformationally mapped to characterize the steric limitations introduced by the added methyl group. Their significant conformers were used as initial structures for docking. Seven monodeoxy methyl a-isomaltosides were also generated based on the methyl a-isomaltoside conformational map and docked to probe the contribution of individual hydroxyl groups to binding. The optimized docking modes are similar for most analogues, and individual atomic energies of intermolecular interaction agree with the assignment of key hydroxyl groups made from kinetic studies.