Virtual screening workflow development guided by the "receiver operating characteristic" curve approach. Application to high-throughput docking on metabotropic glutamate receptor subtype 4.
The "receiver operating characteristic" (ROC) curve method is a well-recognized metric used as an objective way to evaluate the ability of a given test to discriminate between two populations. This facilitates decision-making in a plethora of fields in which a wrong judgment may have serious consequences including clinical diagnosis, public safety, travel security, and economic strategies. When virtual screening is used to speed-up the drug discovery process in pharmaceutical research, taking the right decision upon selecting or discarding a molecule prior to in vitro evaluation is of paramount importance. Characterizing both the ability of a virtual screening workflow to select active molecules and the ability to discard inactive ones, the ROC curve approach is well suited for this critical decision gate. As a case study, the first virtual screening workflow focused on metabotropic glutamate receptor subtype 4 (mGlu4R) agonists is reported here. Six compounds out of 38 selected and tested in vitro were shown to have agonist activity on this target of therapeutic interest.
Triballeau
Nicolas
N
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR8601-CNRS, Université René Descartes-Paris V, 75270 Paris Cedex 06, France. nth@accelrys.com
Acher
Francine
F
Brabet
Isabelle
I
Pin
Jean-Philippe
JP
Bertrand
Hugues-Olivier
HO
D001665:Binding Sites; D016208:Databases, Factual; D015195:Drug Design; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D012372:ROC Curve; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000737:chemistry*
D018094:Receptors, Metabotropic Glutamate; C108823:metabotropic glutamate receptor 4