Enrichment and cross-validation studies of the eHiTS high throughput screening software package

The use of ligand docking tools is well accepted in modern lead discovery. This study examines the eHiTS virtual high throughput screening software, available from SimBioSys Inc., using the DHFR family of proteins. Dihydrofolate reductase (DHFR) was the first enzyme to be targeted for cancer chemotherapy. DHFR is a small enzyme that plays a supporting role, but an essential role, in the building of DNA and other processes. In the eHiTS study, initially, redocking experiments were ran on all the DHFR proteins from homo sapiens. These 15 proteins and associated complexed ligands were then used in a cross-validation experiment, where each ligand was docked against each protein; overlay RMSD values will be presented. Following this, an enrichment study, using ~16,000 similarly sized ligands from the MDDR database, and the set of active ligands from the redocking experiments, was performed. The presentation will present the results from these validation tests.