Subnanomolar Inhibitors from Computer Screening: A Model Study Using Human Carbonic Anhydrase II

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.