Combinatorial computational method gives new picomolar ligands for a known enzyme

Bartosz A. Grzybowski, Alexey V. Ishchenko, Chu Young Kim, George Topalov, Robert Chapman, David W. Christianson, George M. Whitesides, Eugene I. Shakhnovich

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1270-1273
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3
StatePublished - Feb 5 2002
Externally publishedYes

ASJC Scopus subject areas

  • General


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