文摘
The identification of small molecules with selective bioactivity, whether intended as potential therapeuticsor as tools for experimental research, is central to progress in medicine and in the life sciences. To facilitatesuch study, we have developed a ligand-based program well-suited for effective screening of large compoundcollections. This package, MED-SuMoLig, combines a SMARTS-driven substructure search aiming at 3Dpharmacophore profiling and computation of the local atomic density of the compared molecules. Thescreening utility was then investigated using 52 diverse active molecules (against CDK2, Factor Xa, HIV-1protease, neuraminidase, ribonuclease A, and thymidine kinase) merged to a library of about 40 000 putativeinactive (druglike) compounds. In all cases, the program recovered more than half of the actives in the top3% of the screened library. We also compared the performance of MED-SuMoLig with that of ChemMineor of ROCS and found that MED-SuMoLig outperformed both methods for CDK2 and Factor Xa in termsof enrichment rates or performed equally well for the other targets.