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How Reliable Are Current Docking Approaches for Structure‐Based Drug Design? Lessons from Aldose Reductase
Author(s) -
Zentgraf Matthias,
Steuber Holger,
Koch Cornelia,
La Motta Concettina,
Sartini Stefania,
Sotriffer Christoph A.,
Klebe Gerhard
Publication year - 2007
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200603625
Subject(s) - aldose reductase , conformational isomerism , docking (animal) , aldose reductase inhibitor , stereochemistry , chemistry , aldehyde reductase , drug design , sorbinil , binding site , crystallography , enzyme , computational chemistry , biochemistry , medicine , molecule , organic chemistry , nursing
Two related inhibitors were flexibly docked into different conformers of aldose reductase. Although the overall binding topologies were roughly matched, significant deviations are observed in the subsequently determined crystal structures. Flexible redocking into the crystallographically observed protein conformers achieves, however, perfect binding‐position predictions.