FieldScreen: virtual screening using molecular fields. Application to the DUD data set.
FieldScreen, a ligand-based Virtual Screening (VS) method, is described. Its use of 3D molecular fields makes it particularly suitable for scaffold hopping, and we have rigorously validated it for this purpose using a clustered version of the Directory of Useful Decoys (DUD). Using thirteen pharmaceutically relevant targets, we demonstrate that FieldScreen produces superior early chemotype enrichments, compared to DOCK. Additionally, hits retrieved by FieldScreen are consistently lower in molecular weight than those retrieved by docking. Where no X-ray protein structures are available, FieldScreen searches are more robust than docking into homology models or apo structures.
Cheeseright
Timothy J
TJ
Cresset BioMolecular Discovery Ltd., BioPark Hertfordshire, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, United Kingdom. tim@cresset-bmd.com
Mackey
Mark D
MD
Melville
James L
JL
Vinter
Jeremy G
JG
D001665:Binding Sites; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical / Q000706:statistics & numerical data*; D048088:Informatics; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D011506:Proteins / Q000737:chemistry; D013816:Thermodynamics; D014584:User-Computer Interface
D008024:Ligands; D011506:Proteins