Virtual screening workflow development guided by the "receiver operating characteristic" curve approach. Application to high-throughput docking on metabotropic glutamate receptor subtype 4

J Med Chem. 2005 Apr 7;48(7):2534-47. doi: 10.1021/jm049092j.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Databases, Factual
  • Drug Design*
  • Models, Molecular
  • Quantitative Structure-Activity Relationship*
  • ROC Curve*
  • Receptors, Metabotropic Glutamate / agonists*
  • Receptors, Metabotropic Glutamate / chemistry*

Substances

  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 4