caa a22 4500 467938792 CHVBK 20180406153006.0 cr unu---uuuuu 170328e20061201xx s 000 0 eng 10.1007/s10822-006-9091-x doi (NATIONALLICENCE)springer-10.1007/s10822-006-9091-x Ultrafast denovo docking combining pharmacophores and combinatorics [Elektronische Daten] [Marcus Gastreich, Markus Lilienthal, Hans Briem, Holger Claussen] We report on a successful denovo design approach which relies on the combination of multi-million compound combinatorial docking under receptor-based pharmacophore constraints. Inspired by a rationale by A.R. Leach etal., we document on the unification of two steps into one for ligand assembly. In the original work, fragments known to bind in protein active sites were connected forming novel ligand compounds by means of generic skeleton linkers and following a combinatorial approach. In our approach, the knowledge of fragments binding to the protein has been expressed in terms of a receptor-based pharmacophore definition. The combinatorial linking step is performed insitu during docking, starting from combinatorial libraries. Three sample scenarios growing in size and complexity (combinatorial libraries of 1million, 1.3million, and 22.4million compounds) have been created to illustrate the method. Docking could be accomplished between minutes and several hours depending on the outset; the results were throughout promising. Technically, a module compatibility between FlexX C and FlexX-Pharm has been established. The background is explained, and the crucial points from an information scientist's perspective are highlighted. Springer Science+Business Media, LLC, 2007 Combinatorial chemistry nationallicence Docking nationallicence FlexX nationallicence Pharmacophore nationallicence vHTS nationallicence Virtual screening nationallicence Gastreich Marcus BioSolveIT GmbH, An der Ziegelei 75, 53757, St. Augustin, Germany aut Lilienthal Markus BioSolveIT GmbH, An der Ziegelei 75, 53757, St. Augustin, Germany aut Briem Hans CDCC/Computational Chemistry, Schering AG, 13342, Berlin, Germany aut Claussen Holger BioSolveIT GmbH, An der Ziegelei 75, 53757, St. Augustin, Germany aut Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/12(2006-12-01), 717-734 0920-654X 20:12<717 2006 20 10822 https://doi.org/10.1007/s10822-006-9091-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10822-006-9091-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gastreich Marcus BioSolveIT GmbH, An der Ziegelei 75, 53757, St. Augustin, Germany aut NATIONALLICENCE 700 1- Lilienthal Markus BioSolveIT GmbH, An der Ziegelei 75, 53757, St. Augustin, Germany aut NATIONALLICENCE 700 1- Briem Hans CDCC/Computational Chemistry, Schering AG, 13342, Berlin, Germany aut NATIONALLICENCE 700 1- Claussen Holger BioSolveIT GmbH, An der Ziegelei 75, 53757, St. Augustin, Germany aut NATIONALLICENCE 773 0- Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/12(2006-12-01), 717-734 0920-654X 20:12<717 2006 20 10822 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer