Systematic comparison of the performance of different 2D and 3D ligand-based virtual screening methodologies to discover anticonvulsant drugs

MAURICIO DI IANNI; MELISA GANTNER; MARÍA ESPERANZA RUIZ; EDUARDO A. CASTRO; LUIS BRUNO-BLANCH; ALAN TALEVI

COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2015 vol. 18 p. 387 - 398

1386-2073

Virtual screening encompasses a wide range of computational approaches aimed at the high-throughput, cost-efficient exploration of chemical libraries or databases to discover new bioactive compounds or novel medical indications of known drugs. Here, we have developed a systematic comparison of the performance of a large number of 2D and 3D ligand-based approaches (2D and 3D similarity, QSAR models, pharmacophoric hypothesis) in a simulated virtual campaign on a chemical library containing 50 known anticonvulsant drugs and 950 decoys with no previously reported of anticonvulsant effect. To perform such comparison we resorted to ROC curves. We also tested the relative performance of consensus methodologies. Our results indicate that the selective combination of the individual approaches (through voting and ranking combination schemes) significantly outperforms the individual algorithms and/or models.