title: Neuraminidase pharmacophore model derived from diverse classes of inhibitors.
abstract: A three-dimensional pharmacophore model was developed based on 22 currently available inhibitors, which were carefully selected with great diversity in both molecular structure and bioactivity, for discovering new potent neuraminidase (NA) inhibitors to fight against avian influenza virus. The best hypothesis (Hypo1), consisting of five features, namely, one positive ionizable group, one negative ionizable group, one hydrophobic point, and two hydrogen-bond donors, has a correlation coefficient of 0.902, a root mean square deviation of 1.392, and a cost difference of 72.88, suggesting that a highly predictive pharmacophore model was successfully obtained. The application of the model shows great success in predicting the activities of 88 known NA inhibitors in our test set with a correlation coefficient of 0.818 with a cross-validation of 98% confidence level. Accordingly, our model should be reliable in identifying structurally diverse compounds with desired biological activity.
authors.affiliation: Drug Discovery and Design Centre, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, and Graduate School, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: KunQian
authors.initials: K
authors.lastname: Yu
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology*; D008954:Models, Biological; D008956:Models, Chemical; D008968:Molecular Conformation; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D009439:Neuraminidase