Parallel screening: a novel concept in pharmacophore modeling and virtual screening.
Parallel screening comprises a novel in silico method to predict the potential biological activities of a compound by screening it with a multitude of pharmacophore models. Our aim is to provide a fast, large-scale system that allows for virtual activity profiling. In this proof of principle study, carried out with the software tools LigandScout and Catalyst, we present a model work for the application of parallel pharmacophore-based virtual screening on a set of 50 structure-based pharmacophore models built for various viral targets and 100 antiviral compounds. The latter were screened against all pharmacophore models in order to determine if their biological targets could be correctly predicted via an enrichment of corresponding pharmacophores matching these ligands. The results demonstrate that the desired enrichment, that is, successful virtual activity profiling, was achieved for approximately 90% of all input molecules. We discuss descriptors for output validation, as well as various aspects influencing the analysis of the obtained activity profiles, and the effect of the utilized search modus for screening.
Steindl
Theodora M
TM
Institute of Pharmacy, Computer Aided Molecular Design Group, University of Innsbruck, Innrain 52c, Austria.
Schuster
Daniela
D
Laggner
Christian
C
Langer
Thierry
T
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D008958:Models, Molecular
D000998:Antiviral Agents