TY - JOUR
T1 - Combinatorial computational method gives new picomolar ligands for a known enzyme
AU - Grzybowski, Bartosz A.
AU - Ishchenko, Alexey V.
AU - Kim, Chu Young
AU - Topalov, George
AU - Chapman, Robert
AU - Christianson, David W.
AU - Whitesides, George M.
AU - Shakhnovich, Eugene I.
PY - 2002/2/5
Y1 - 2002/2/5
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.032673399
DO - 10.1073/pnas.032673399
M3 - Article
C2 - 11818565
AN - SCOPUS:0037022302
SN - 0027-8424
VL - 99
SP - 1270
EP - 1273
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 3
ER -