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dc.contributor.author
Schneider, Gisbert
dc.contributor.author
Hartenfeller, Markus
dc.contributor.author
Zettl, Heiko
dc.contributor.author
Walter, Miriam
dc.contributor.author
Rupp, Matthias
dc.contributor.author
Reisen, Felix
dc.contributor.author
Proschak, Ewgenij
dc.contributor.author
Weggen, Sascha
dc.contributor.author
Stark, Holger
dc.date.accessioned
2019-01-17T15:01:41Z
dc.date.available
2017-06-09T20:10:40Z
dc.date.available
2019-01-17T15:01:41Z
dc.date.issued
2012-02-16
dc.identifier.issn
1553-734X
dc.identifier.issn
1553-7358
dc.identifier.other
10.1371/journal.pcbi.1002380
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/47349
dc.identifier.doi
10.3929/ethz-b-000047349
dc.description.abstract
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.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.title
DOGS: Reaction-Driven de novo Design of Bioactive Compounds
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
ethz.journal.title
PLoS Computational Biology
ethz.journal.volume
8
en_US
ethz.journal.issue
2
en_US
ethz.journal.abbreviated
PLOS comput. biol.
ethz.pages.start
e1002380
en_US
ethz.size
12 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
005410277
ethz.publication.place
San Francisco, CA, USA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03852 - Schneider, Gisbert / Schneider, Gisbert
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03852 - Schneider, Gisbert / Schneider, Gisbert
ethz.date.deposited
2017-06-09T20:13:54Z
ethz.source
ECIT
ethz.identifier.importid
imp59364f120dd3347675
ethz.ecitpid
pub:77902
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-26T05:24:59Z
ethz.rosetta.lastUpdated
2019-01-17T15:01:50Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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