Abstract
Monte Carlo (MC)-extended linear response (ELR) calculations have been used for prediction of binding affinities of celecoxib analogues with the COX-2 enzyme. Three physically motivated descriptors from the MC simulations were used in a regression equation to fit 45 experimental activities with r(2)=0.71 and q(2)=0.68. The ELR approach provides a promising screen for optimization of enzyme inhibitors.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Algorithms
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Celecoxib
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Combinatorial Chemistry Techniques
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / chemical synthesis
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Cyclooxygenase Inhibitors / chemistry*
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Cyclooxygenase Inhibitors / pharmacology*
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Electrochemistry
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Isoenzymes / metabolism*
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Linear Models
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Models, Chemical
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Monte Carlo Method
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Pyrazoles
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Structure-Activity Relationship
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Sulfonamides / chemistry*
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Sulfonamides / pharmacology*
Substances
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Isoenzymes
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Pyrazoles
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Sulfonamides
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases
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Celecoxib