文献类型：期刊文献

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

作者：Chen, Zhi[2];Li, Hong-lin[1];Zhang, Qi-jun[2];Bao, Xiao-guang[2];Yu, Kun-qian[2];Luo, Xiao-min[2];Zhu, Wei-liang[2];Jiang, Hua-liang[1,2]

机构：[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

年份：2009

卷号：30

期号：12

起止页码：1694

外文期刊名：ACTA PHARMACOLOGICA SINICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000273048500014)】；

基金：We thank the Shanghai Supercomputing Center and Computer Network Information Center of Chinese Academy of Sciences for allocation of computing time. This work was supported by the National Natural Science Foundation of China (grants 20721003, 20803022, and 30672539), the International Collaboration Projects (grants 2007DFB30370 and 20720102040), the 863 Hi-Tech Program of China (grant 2007AA02Z304), and the State Key Program of Basic Research of China (grants 2009CB918502 and 2009CB918501).

语种：英文

外文关键词：pharmacophore; docking; LigandScout; enrichment; hit rate

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.