caa a22 4500 378911201 CHVBK 20180305123542.0 cr unu---uuuuu 161128e20040101xx s 000 0 eng 10.1351/pac200476050991 doi (NATIONALLICENCE)gruyter-10.1351/pac200476050991 Virtual combinatorial chemistry and in silico screening: Efficient tools for lead structure discovery? [Elektronische Daten] [Thierry Langer, G. Wolber] In this article, an overview of the most common ligand-based in silico screening techniques is given together with an example on the recent successful application of combined use of pharmacophore modeling, database mining, and biological assays. Additionally, a new approach for structure-based high-throughput pharmacophore model generation is presented. The LigandScout program contains an automated method for creating pharmacophore models from experimentally determined structure data, e.g., publicly available from the Brookhaven Protein Databank (PDB). In a first step, known algorithms were implemented and improved to extract small-molecule ligands from the PDB including assignment of hybridization states and bond orders. Second, from the interactions of the interpreted ligands with relevant surrounding amino acids, pharmacophore models reflecting functional interactions like H-bonds or ionic transfer interactions were created. These models can be used for screening molecular databases for similar modes of actions on the one hand, or for screening one single compound for potential side-effects (reversed screening) on the other hand. The implementation was done using the ilib framework, which also formed the basis of the software tool CombiGen, a fragment-based virtual combinatorial library generation program enabling the user to obtain in silico compound collections with high drug-likeness. © 2013 Walter de Gruyter GmbH, Berlin/Boston Langer Thierry Institute of Pharmacy, University of Innsbruck Innrain 52, A-6020 Innsbruck, Austria; Inte:Ligand GmbH Clemens-Maria Hofbauer-G.6, A-2344 Maria Enzersdorf, Austria aut Wolber G. Institute of Pharmacy, University of Innsbruck Innrain 52, A-6020 Innsbruck, Austria; Inte:Ligand GmbH Clemens-Maria Hofbauer-G.6, A-2344 Maria Enzersdorf, Austria aut Pure and Applied Chemistry De Gruyter 76/5(2004-01-01), 991-996 0033-4545 76:5<991 2004 76 pac https://doi.org/10.1351/pac200476050991 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1351/pac200476050991 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Langer Thierry Institute of Pharmacy, University of Innsbruck Innrain 52, A-6020 Innsbruck, Austria; Inte:Ligand GmbH Clemens-Maria Hofbauer-G.6, A-2344 Maria Enzersdorf, Austria aut NATIONALLICENCE 700 1- Wolber G. Institute of Pharmacy, University of Innsbruck Innrain 52, A-6020 Innsbruck, Austria; Inte:Ligand GmbH Clemens-Maria Hofbauer-G.6, A-2344 Maria Enzersdorf, Austria aut NATIONALLICENCE 773 0- Pure and Applied Chemistry De Gruyter 76/5(2004-01-01), 991-996 0033-4545 76:5<991 2004 76 pac CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter