A comparison of ligand based virtual screening methods and application to corticotropin releasing factor 1 receptor
Ligand based virtual screening approaches were applied to the CRF1 receptor. We compared ECFP6 fingerprints, FTrees, Topomers, Cresset FieldScreen, ROCS OpenEye shape Tanimoto, OpenEye combo-score and OpenEye electrostatics. The 3D methods OpenEye Shape Tanimoto, combo-score and Topomers performed the best at separating actives from inactives in retrospective experiments. By virtue of their higher enrichment the same methods identified more active scaffolds. However, amongst a given number of active compounds the Cresset and OpenEye electrostatic methods contained more scaffolds and returned ranked compounds with greater diversity. A selection of the methods were employed to recommend compounds for screening in a prospective experiment. New CRF1 actives antagonists were found. The new actives contained different underlying chemical architecture to the query molecules, results indicative of successful scaffold-hopping.
ligand based virtual screening corticotropin releasing factor crf1 crh1 scaffold-hopping