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Subnanomolar Inhibitors from Computer Screening: A Model Study Using Human Carbonic Anhydrase II
Author(s) -
Grüneberg Sven,
Wendt Bernd,
Klebe Gerhard
Publication year - 2001
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 - 10.1002/1521-3773(20010119)40:2<389::aid-anie389>3.0.co;2-#
Subject(s) - carbonic anhydrase , carbonic anhydrase ii , chemistry , biochemistry , combinatorial chemistry , enzyme
FlexX and DrugScore are the two computer programs which were applied finally to search for inhibitors of the enzyme carbonic anhydrase II in compound libraries and to predict their binding properties. Subsequently the actual binding affinities of 13 of the best‐ranked compounds discovered in this way were measured experimentally. Three of these proved to be subnanomolar, one nanomolar, and seven micromolar inhibitors. The predicted binding mode was confirmed crystallographically for two of the inhibitors.