title: Estimation of binding affinities for celecoxib analogues with COX-2 via Monte Carlo-extended linear response.
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.
authors.affiliation: Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Wesolowski
authors.forename: William L
authors.initials: WL
authors.lastname: Jorgensen
mesh_terms: D000465:Algorithms; D000068579:Celecoxib; D020650:Combinatorial Chemistry Techniques; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004563:Electrochemistry; D007527:Isoenzymes / Q000378:metabolism*; D016014:Linear Models; D008956:Models, Chemical; D009010:Monte Carlo Method; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011720:Pyrazoles; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib