Comparison of automated docking programs as virtual screening tools.
The performance of several commercially available docking programs is compared in the context of virtual screening. Five different protein targets are used, each with several known ligands. The simulated screening deck comprised 1000 molecules from a cleansed version of the MDL drug data report and 49 known ligands. For many of the known ligands, crystal structures of the relevant protein-ligand complexes were available. We attempted to run experiments with each docking method that were as similar as possible. For a given docking method, hit rates were improved versus what would be expected for random selection for most protein targets. However, the ability to prioritize known ligands on the basis of docking poses that resemble known crystal structures is both method- and target-dependent.
Cummings
Maxwell D
MD
Johnson & Johnson Pharmaceutical Research & Development, Eagleview Corporate Center, 665 Stockton Drive, Exton, Pennsylvania 19341, USA. mcumming@prdus.jnj.com
DesJarlais
Renee L
RL
Gibbs
Alan C
AC
Mohan
Venkatraman
V
Jaeger
Edward P
EP
D001665:Binding Sites; D016333:HIV Protease / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry; D011485:Protein Binding; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D011518:Proto-Oncogene Proteins / Q000737:chemistry; D051736:Proto-Oncogene Proteins c-mdm2; D021281:Quantitative Structure-Activity Relationship; D012984:Software; D013917:Thrombin / Q000737:chemistry; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry
D008024:Ligands; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D013917:Thrombin; D014568:Urokinase-Type Plasminogen Activator; D016333:HIV Protease