DOGS : Reaction-Driven de novo Design of Bioactive Compounds

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HARTENFELLER, Markus, Heiko ZETTL, Miriam WALTER, Matthias RUPP, Felix REISEN, Ewgenij PROSCHAK, Sascha WEGGEN, Holger STARK, Gisbert SCHNEIDER, 2012. DOGS : Reaction-Driven de novo Design of Bioactive Compounds. In: PLoS Computational Biology. Public Library of Science (PLoS). 8(2), e1002380. ISSN 1553-734X. eISSN 1553-7358. Available under: doi: 10.1371/journal.pcbi.1002380

@article{Hartenfeller2012React-52832, title={DOGS : Reaction-Driven de novo Design of Bioactive Compounds}, year={2012}, doi={10.1371/journal.pcbi.1002380}, number={2}, volume={8}, issn={1553-734X}, journal={PLoS Computational Biology}, author={Hartenfeller, Markus and Zettl, Heiko and Walter, Miriam and Rupp, Matthias and Reisen, Felix and Proschak, Ewgenij and Weggen, Sascha and Stark, Holger and Schneider, Gisbert}, note={Article Number: e1002380} }

<rdf:RDF xmlns:dcterms="" xmlns:dc="" xmlns:rdf="" xmlns:bibo="" xmlns:dspace="" xmlns:foaf="" xmlns:void="" xmlns:xsd="" > <rdf:Description rdf:about=""> <dc:contributor>Proschak, Ewgenij</dc:contributor> <dcterms:rights rdf:resource=""/> <dc:creator>Hartenfeller, Markus</dc:creator> <dcterms:hasPart rdf:resource=""/> <dc:creator>Reisen, Felix</dc:creator> <dc:creator>Walter, Miriam</dc:creator> <dc:language>eng</dc:language> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:date rdf:datatype="">2021-02-15T10:22:50Z</dc:date> <dc:contributor>Schneider, Gisbert</dc:contributor> <dc:creator>Zettl, Heiko</dc:creator> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:contributor>Stark, Holger</dc:contributor> <dcterms:abstract xml:lang="eng">We present a computational method for the reaction-based de novo design of drug-like molecules. The software DOGS (Design of Genuine Structures) features a ligand-based strategy for automated 'in silico' assembly of potentially novel bioactive compounds. The quality of the designed compounds is assessed by a graph kernel method measuring their similarity to known bioactive reference ligands in terms of structural and pharmacophoric features. We implemented a deterministic compound construction procedure that explicitly considers compound synthesizability, based on a compilation of 25'144 readily available synthetic building blocks and 58 established reaction principles. This enables the software to suggest a synthesis route for each designed compound. Two prospective case studies are presented together with details on the algorithm and its implementation. De novo designed ligand candidates for the human histamine H₄ receptor and γ-secretase were synthesized as suggested by the software. The computational approach proved to be suitable for scaffold-hopping from known ligands to novel chemotypes, and for generating bioactive molecules with drug-like properties.</dcterms:abstract> <dc:contributor>Zettl, Heiko</dc:contributor> <dc:creator>Schneider, Gisbert</dc:creator> <dc:rights>Attribution 4.0 International</dc:rights> <dspace:isPartOfCollection rdf:resource=""/> <dspace:hasBitstream rdf:resource=""/> <dc:creator>Stark, Holger</dc:creator> <dc:contributor>Rupp, Matthias</dc:contributor> <dc:contributor>Walter, Miriam</dc:contributor> <dcterms:available rdf:datatype="">2021-02-15T10:22:50Z</dcterms:available> <dc:contributor>Weggen, Sascha</dc:contributor> <dcterms:issued>2012</dcterms:issued> <dc:creator>Rupp, Matthias</dc:creator> <dcterms:isPartOf rdf:resource=""/> <bibo:uri rdf:resource=""/> <dc:contributor>Reisen, Felix</dc:contributor> <dc:contributor>Hartenfeller, Markus</dc:contributor> <dc:creator>Weggen, Sascha</dc:creator> <dcterms:title>DOGS : Reaction-Driven de novo Design of Bioactive Compounds</dcterms:title> <dc:creator>Proschak, Ewgenij</dc:creator> </rdf:Description> </rdf:RDF>

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