Structural features of falcipain-3 inhibitors: an in silico study

	Structural features of falcipain-3 inhibitors: an in silico study
	Wang, Jinghui 1; Li, Feng 2; Li, Yan 1; Yang, Yinfeng 1; Zhang, Shuwei 1; Yang, Ling 3
刊名	molecular biosystems
	2013
卷号	9 期号:9 页码:2296-2310
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.
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
收录类别	SCI
语种	英语
WOS记录号	WOS:000322447600011
公开日期	2015-11-10
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/137903]
专题	大连化学物理研究所_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
推荐引用方式 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.