Fast structure-based virtual ligand screening combining FRED, DOCK, and Surflex.
A protocol was devised in which FRED, DOCK, and Surflex were combined in a multistep virtual ligand screening (VLS) procedure to screen the pocket of four different proteins. One goal was to evaluate the impact of chaining "freely available packages to academic users" on docking/scoring accuracy and CPU time consumption. A bank of 65 660 compounds including 49 known actives was generated. Our procedure is successful because docking/scoring parameters are tuned according to the nature of the binding pocket and because a shape-based filtering tool is applied prior to flexible docking. The obtained enrichment factors are in line with those reported in recent studies. We suggest that consensus docking/scoring could be valuable to some drug discovery projects. The present protocol could process the entire bank for one receptor in less than a week on one processor, suggesting that VLS experiments could be performed even without large computer resources.
Miteva
Maria A
MA
INSERM U648, University Paris 5, Paris 75006, France.
Lee
Wen H
WH
Montes
Matthieu O
MO
Villoutreix
Bruno O
BO
D001665:Binding Sites; D016208:Databases, Factual; D015942:Factor VIIa / Q000737:chemistry; D008024:Ligands; D015394:Molecular Structure; D009439:Neuraminidase / Q000737:chemistry; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D011960:Receptors, Estrogen / Q000737:chemistry; D013937:Thymidine Kinase / Q000737:chemistry
D008024:Ligands; D011960:Receptors, Estrogen; D013937:Thymidine Kinase; D009439:Neuraminidase; D015942:Factor VIIa