Discovery of FIXa inhibitors by combination of pharmacophore modeling, molecular docking, and 3D-QSAR modeling

被引:6
|
作者
Li, Penghua [1 ]
Peng, Jiale [1 ]
Zhou, Yeheng [1 ]
Li, Yaping [1 ]
Liu, XingYong [1 ]
Wang, LiangLiang [2 ,3 ]
Zuo, ZhiLi [2 ,3 ]
机构
[1] Sichuan Univ Sci & Engn, Sch Chem Engn, Zigong, Peoples R China
[2] Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Yunnan, Peoples R China
[3] Yunnan Key Lab Nat Med Chem, Kunming, Yunnan, Peoples R China
基金
中国国家自然科学基金;
关键词
Pharmacophore; molecular docking; 3D-QSAR; FIXa; antithrombotic; FACTOR IXA INHIBITORS; ANTICOAGULANTS; POTENT; DERIVATIVES; IDENTIFICATION; SIMULATION; THROMBOSIS; ALIGNMENT; BINDING; KINASE;
D O I
10.1080/10799893.2018.1468784
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human Coagulation Factor IXa (FIXa), specifically inhibited at the initiation stage of the blood coagulation cascade, is an excellent target for developing selective and safe anticoagulants. To explore this inhibitory mechanism, 86 FIXa inhibitors were selected to generate pharmacophore models and subsequently SAR models. Both best pharmacophore model and ROC curve were built through the Receptor-Ligand Pharmacophore Generation module. CoMFA model based on molecular docking and PLS factor analysis methods were developed. Model propagations values are q(2) = 0.709, r(2) = 0.949, and r(pred)(2) = 0.905. The satisfactory q(value)(2) of 0.609, r(value)(2) of 0.962, and rpred(2 )value of 0.819 for CoMSIA indicated that the CoMFA and CoMSIA models are both available to predict the inhibitory activity on FIXa. On the basis of pharmacophore modeling, molecular docking, and 3D-QSAR modeling screening, six molecules are screened as potential FIXa inhibitors.
引用
收藏
页码:213 / 224
页数:12
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