Combinatorial computational method gives new picomolar ligands for a known enzyme
Open Access
- 29 January 2002
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 99 (3) , 1270-1273
- https://doi.org/10.1073/pnas.032673399
Abstract
Combinatorial small molecule growth algorithm was used to design inhibitors for human carbonic anhydrase II. Two enantiomeric candidate molecules were predicted to bind with high potency (with R isomer binding stronger than S), but in two distinct conformations. The experiments verified that computational predictions concerning the binding affinities and the binding modes were correct for both isomers. The designed R isomer is the best-known inhibitor (Kd ∼ 30 pM) of human carbonic anhydrase II.Keywords
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