Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets

doi:10.1038/aps.2009.159

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	Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets
	Chen, Zhi 2; Li, Hong-lin 1; Zhang, Qi-jun 2; Bao, Xiao-guang 2; Yu, Kun-qian2 ; Luo, Xiao-min2 ; Zhu, Wei-liang2 ; Jiang, Hua-liang1,2
刊名	ACTA PHARMACOLOGICA SINICA
	2009-12
卷号	30 期号:12 页码:1694-1708
关键词	pharmacophore docking LigandScout enrichment hit rate
ISSN号	1671-4083
DOI	10.1038/aps.2009.159
文献子类	Article
英文摘要	Aim: This study was conducted to compare the efficiencies of two virtual screening approaches, pharmacophore-based virtual screening (PBVS) and docking-based virtual screening (DBVS) methods. Methods: All virtual screens were performed on two data sets of small molecules with both actives and decoys against eight structurally diverse protein targets, namely angiotensin converting enzyme (ACE), acetylcholinesterase (AChE), androgen receptor (AR), D-alanyl-D-alanine carboxypeptidase (DacA), dihydrofolate reductase (DHFR), estrogen receptors a (ER alpha), HIV-1 protease (HIV-pr), and thymidine kinase (TK). Each pharmacophore model was constructed based on several X-ray structures of protein-ligand complexes. Virtual screens were performed using four screening standards, the program Catalyst for PBVS and three docking programs (DOCK, GOLD and Glide) for DBVS. Results: Of the sixteen sets of virtual screens (one target versus two testing databases), the enrichment factors of fourteen cases using the PBVS method were higher than those using DBVS methods. The average hit rates over the eight targets at 2% and 5% of the highest ranks of the entire databases for PBVS are much higher than those for DBVS. Conclusion: The PBVS method outperformed DBVS methods in retrieving actives from the databases in our tested targets, and is a powerful method in drug discovery.
资助项目	Shanghai Supercomputing Center[00000000] ; Computer Network Information Center of Chinese Academy of Sciences[00000000] ; National Natural Science Foundation of China[20721003] ; National Natural Science Foundation of China[20803022] ; National Natural Science Foundation of China[30672539] ; International Collaboration[2007DFB30370] ; International Collaboration[20720102040] ; 863 Hi-Tech Program of China[2007AA02Z304] ; State Key Program of Basic Research of China[2009CB918502] ; State Key Program of Basic Research of China[2009CB918501]
WOS关键词	ANGIOTENSIN-CONVERTING ENZYME ; AUTOMATED MOLECULAR DOCKING ; DRUG DISCOVERY ; GENETIC ALGORITHM ; HIGH-THROUGHPUT ; LIGAND DOCKING ; INHIBITORS ; DESIGN ; STRATEGIES ; RECEPTOR
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:3798142
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000273048500014
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279068]
专题	药物发现与设计中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Li, Hong-lin
作者单位	1.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Chen, Zhi,Li, Hong-lin,Zhang, Qi-jun,et al. Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets[J]. ACTA PHARMACOLOGICA SINICA,2009,30(12):1694-1708.
APA	Chen, Zhi.,Li, Hong-lin.,Zhang, Qi-jun.,Bao, Xiao-guang.,Yu, Kun-qian.,...&Jiang, Hua-liang.(2009).Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets.ACTA PHARMACOLOGICA SINICA,30(12),1694-1708.
MLA	Chen, Zhi,et al."Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets".ACTA PHARMACOLOGICA SINICA 30.12(2009):1694-1708.