Parallel screening and activity profiling with HIV protease inhibitor pharmacophore models.
Parallel Screening has been introduced as an in silico method to predict the potential biological activities of compounds by screening them with a multitude of pharmacophore models. This study presents an early application example employing a Pipeline Pilot-based screening platform for automatic large-scale virtual activity profiling. An extensive set of HIV protease inhibitor pharmacophore models was used to screen a selection of active and inactive compounds. Furthermore, we aimed to address the usually critically eyed point, whether it is possible in a parallel screening system to differentiate between similar molecules/molecules acting on closely related proteins, and therefore we incorporated a collection of other protease inhibitors including aspartic protease inhibitors. The results of the screening experiments show a clear trend toward most extensive retrieval of known active ligands, followed by the general protease inhibitors and lowest recovery of inactive compounds.
Steindl
Theodora M
TM
Institute of Pharmacy, Computer Aided Molecular Design Group, University of Innsbruck, Innrain 52c and Center for Molecular Biosciences Innsbruck (CMBI), Peter-Mair-Strasse 1, A-6020 Innsbruck, Austria. theodora.steindl@uibk.ac.at
Schuster
Daniela
D
Laggner
Christian
C
Chuang
Karen
K
Hoffmann
Rémy D
RD
Langer
Thierry
T
D019295:Computational Biology; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary
D017320:HIV Protease Inhibitors; D016333:HIV Protease