title: A unified and quantitative receptor model for the microtubule binding of paclitaxel and epothilone.
abstract: [formula: see text] Paclitaxel and epothilone represent the two major classes of antimicrotubule agents that promote tubulin polymerization and, presumably, mitotic arrest during cell division. A common minireceptor binding site model at beta-tubulin has been constructed for these structurally divergent compounds. Utilizing 20 amino acids identified in photoaffinity labeling experiments, the 3-D model correlates measured and predicted Ki's with r = 0.99 and rms(delta Gcalc-delta Gexp) = 0.2 kcal/mol. In addition, the model predicts the affinity of compounds not used in the training set and explains much of the SAR for the paclitaxel and epothilone families.
authors.affiliation: Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Xia
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.forename: D
authors.initials: D
authors.lastname: Hwang
authors.forename: J M
authors.initials: JM
authors.lastname: Jansen
authors.forename: M
authors.initials: M
authors.lastname: Botta
authors.forename: D C
authors.initials: DC
authors.lastname: Liotta
authors.forename: J P
authors.initials: JP
authors.lastname: Snyder
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D034261:Epothilones; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009010:Monte Carlo Method; D017239:Paclitaxel / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011955:Receptors, Drug / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism*; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; D004852:Epoxy Compounds; D011955:Receptors, Drug; D013844:Thiazoles; D014404:Tubulin; D017239:Paclitaxel; C093788:epothilone B