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Structural features of falcipain-3 inhibitors: an in silico study
Wang, Jinghui1; Li, Feng2; Li, Yan1; Yang, Yinfeng1; Zhang, Shuwei1; Yang, Ling3
刊名MOLECULAR BIOSYSTEMS
2013
DOI10.1039/c3mb70105k
9期:9页:2296-2310
收录类别SCI
文章类型Article
WOS标题词Science & Technology ; Life Sciences & Biomedicine
类目[WOS]Biochemistry & Molecular Biology
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]MOLECULAR DOCKING ; PLASMODIUM-FALCIPARUM ; CYSTEINE PROTEASES ; QUANTITATIVE STRUCTURE ; RATIONAL SELECTION ; MALARIA PARASITES ; COMBINED 3D-QSAR ; QSAR MODELS ; DRUG DESIGN ; TEST SETS
英文摘要Falcipain-3, the major cysteine hemoglobinase from the human malaria parasite Plasmodium falciparum, is critical for parasite development and is considered as a promising chemotherapeutic target. In order to understand the structure-activity correlation of falcipain-3 inhibitors, a set of ligand-and receptor-based 3D-QSAR models were developed in the present work employing comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for 247 2-pyrimidinecarbonitrile derivatives. An optimum ligand-based CoMSIA model yielded a cross validation Q(2) = 0.501, non-cross validation R-ncv(2) = 0.821 and predictive R-pred(2) = 0.750. In addition, docking analysis and molecular dynamics simulation were applied to elucidate the probable binding modes of the ligand in the falcipain-3 binding pocket. Graphic representation of the results, as contoured 3D coefficient plots, also provides a clue to the reasonable modification of molecules. (1) Bulky substituents at the 3-position, and rings B and D increase the biological activity; (2) electrostatic groups at rings B, C and D are likely helpful to increase the falcipain-3 inhibition; (3) hydrophobic groups at rings B and D are favored; (4) Gly92, Ile94 and Thr95 which formed several H-bonds and a water-bridged H-bond are crucial for falcipain-3 inhibitors. This model, we hope, will be of help in designing and predicting novel falcipain-3 inhibitors.
语种英语
WOS记录号WOS:000322447600011
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/137903
专题中国科学院大连化学物理研究所
作者单位1.Dalian Univ Technol, MOE, Key Lab Ind Ecol & Environm Engn, Dalian 116024, Liaoning, Peoples R China
2.Henan Inst Engn, Dept Civil Engn, Zhengzhou 451191, Henan, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, Grad Sch, Lab Pharmaceut Resource Discovery, Dalian 116023, Liaoning, Peoples R China
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GB/T 7714
Wang, Jinghui,Li, Feng,Li, Yan,et al. Structural features of falcipain-3 inhibitors: an in silico study[J]. MOLECULAR BIOSYSTEMS,2013,9(9):2296-2310.
APA Wang, Jinghui,Li, Feng,Li, Yan,Yang, Yinfeng,Zhang, Shuwei,&Yang, Ling.(2013).Structural features of falcipain-3 inhibitors: an in silico study.MOLECULAR BIOSYSTEMS,9(9),2296-2310.
MLA Wang, Jinghui,et al."Structural features of falcipain-3 inhibitors: an in silico study".MOLECULAR BIOSYSTEMS 9.9(2013):2296-2310.
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