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Force calculations in automated docking: Enzyme–substrate interactions in Fusarium oxysporum Cel7B
Author(s) -
Mulakala Chandrika,
Reilly Peter J.
Publication year - 2005
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/prot.20632
Subject(s) - autodock , chemistry , active site , docking (animal) , stereochemistry , hydrogen bond , residue (chemistry) , enzyme , molecule , biochemistry , organic chemistry , in silico , medicine , nursing , gene
AutoDock is a small‐molecule docking program that uses an energy function to score docked ligands. Here AutoDock's grid‐based method for energy evaluation was exploited to evaluate the force exerted by Fusarium oxysporum Cel7B on the atoms of docked cellooligosaccharides and a thiooligosaccharide substrate analog. Coupled with the interaction energies evaluated for each docked ligand, these forces give insight into the dynamics of the ligand in the active site, and help to elucidate the relative importance of specific enzyme–substrate interactions in stabilizing the substrate transition‐state conformation. The processive force on the docked substrate in the F. oxysporum Cel7B active site is less than half of that on the docked substrate in the Hypocrea jecorina Cel7A active site. Hydrogen bonding interactions of the enzyme with the C2 hydroxyl group of the glucosyl residue in subsite −2 and with the C3 hydroxyl group of the glucosyl residue in subsite +1 are the most significant in stabilizing the distorted1, 4 B transition‐state conformation of the glucosyl residue in subsite −1. The force calculations also help to elucidate the mechanism that prevents the active site from fouling. Proteins 2005. © 2005 Wiley‐Liss, Inc.