Combinatorial computational method gives new picomolar ligands for a known enzyme
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Date
2002
Author(s)
Grzybowski, Bartosz A.
Ishchenko, Alexey V.
Kim, Chu-Young
Topalov, George
Chapman, Robert
Christianson, David W.
Whitesides, George M.
Shakhnovich, Eugene I.
Publisher
National Academy of Sciences
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Citation
Grzybowski, B. A., A. V. Ishchenko, C.-Y. Kim, G. Topalov, R. Chapman, D. W. Christianson, G. M. Whitesides, and E. I. Shakhnovich. 2002. “Combinatorial Computational Method Gives New Picomolar Ligands for a Known Enzyme.” Proceedings of the National Academy of Sciences99 (3): 1270–73. 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 (K-d similar to 30 pM) of human carbonic anhydrase II.
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