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题名: Structural features of falcipain-3 inhibitors: an in silico study
作者: Wang, Jinghui1;  Li, Feng2;  Li, Yan1;  Yang, Yinfeng1;  Zhang, Shuwei1;  Yang, Ling3
刊名: MOLECULAR BIOSYSTEMS
发表日期: 2013
DOI: 10.1039/c3mb70105k
卷: 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
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.
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
语种: 英语
WOS记录号: WOS:000322447600011
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/137903
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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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

Recommended Citation:
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.
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