title: Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets.
abstract: OBJECTIVE
  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 alpha (ERalpha), 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.
  
  
  CONCLUSIONS
  The PBVS method outperformed DBVS methods in retrieving actives from the databases in our tested targets, and is a powerful method in drug discovery.
authors: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors: Zhi
authors: Z
authors: Chen
authors: Hong-lin
authors: HL
authors: Li
authors: Qi-jun
authors: QJ
authors: Zhang
authors: Xiao-guang
authors: XG
authors: Bao
authors: Kun-qian
authors: KQ
authors: Yu
authors: Xiao-min
authors: XM
authors: Luo
authors: Wei-liang
authors: WL
authors: Zhu
authors: Hua-liang
authors: HL
authors: Jiang
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D016208:Databases, Factual; D015195:Drug Design; D015497:HIV-1; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011506:Proteins; D012984:Software
chemical_list: D008024:Ligands; D011506:Proteins