Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets.
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.
Chen
Zhi
Z
Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Li
Hong-lin
HL
Zhang
Qi-jun
QJ
Bao
Xiao-guang
XG
Yu
Kun-qian
KQ
Luo
Xiao-min
XM
Zhu
Wei-liang
WL
Jiang
Hua-liang
HL
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
D008024:Ligands; D011506:Proteins