A predictive pharmacophore model has been generated from a series of diverse fatty acid amide hydrolase(FAAH)inhibitors and the optimal pharmacophore model applied in virtual screening.The pharmacophore model was base...A predictive pharmacophore model has been generated from a series of diverse fatty acid amide hydrolase(FAAH)inhibitors and the optimal pharmacophore model applied in virtual screening.The pharmacophore model was based on a training set of 21 compounds carefully selected from the published literatures.The optimal model Hypo-1 included four features(two hydrogen-bond acceptor units,one aromatic hydrophobic unit and one aromatic ring unit)and two excluded volumes.Cross-validation of the model confirmed that Hypo-1 was not generated by chance correlation.A large test set of 55 compounds showed that Hypo-1 performed well in classifying highly active and less active FAAH inhibitors.Superimposition analysis of the FAAH X-ray crystal structure and the pharmacophore Hypo-1 further validated the adequacy of the model.Virtual screening generated a total of 976 hits from the Zinc Natural Products database,a hit rate of 1.04%and enrichment of 83.89.The acceptable hit rate further supports the use of Hypo-1 as a 3D query tool for virtual screening.展开更多
基金supported by the National Science Foundation of China(Grant No.40976050)。
文摘A predictive pharmacophore model has been generated from a series of diverse fatty acid amide hydrolase(FAAH)inhibitors and the optimal pharmacophore model applied in virtual screening.The pharmacophore model was based on a training set of 21 compounds carefully selected from the published literatures.The optimal model Hypo-1 included four features(two hydrogen-bond acceptor units,one aromatic hydrophobic unit and one aromatic ring unit)and two excluded volumes.Cross-validation of the model confirmed that Hypo-1 was not generated by chance correlation.A large test set of 55 compounds showed that Hypo-1 performed well in classifying highly active and less active FAAH inhibitors.Superimposition analysis of the FAAH X-ray crystal structure and the pharmacophore Hypo-1 further validated the adequacy of the model.Virtual screening generated a total of 976 hits from the Zinc Natural Products database,a hit rate of 1.04%and enrichment of 83.89.The acceptable hit rate further supports the use of Hypo-1 as a 3D query tool for virtual screening.
