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. 2013 Jan;41(Database issue):D1137-43.
doi: 10.1093/nar/gks1059. Epub 2012 Nov 17.

SwissBioisostere: a database of molecular replacements for ligand design

Matthias Wirth  1 , Vincent Zoete, Olivier Michielin, Wolfgang H B Sauer
Affiliations

SwissBioisostere: a database of molecular replacements for ligand design

Matthias Wirth et al. Nucleic Acids Res. 2013 Jan.

Abstract

The SwissBioisostere database (http://www.swissbioisostere.ch) contains information on molecular replacements and their performance in biochemical assays. It is meant to provide researchers in drug discovery projects with ideas for bioisosteric modifications of their current lead molecule, as well as to give interested scientists access to the details on particular molecular replacements. As of August 2012, the database contains 21,293,355 datapoints corresponding to 5,586,462 unique replacements that have been measured in 35,039 assays against 1948 molecular targets representing 30 target classes. The accessible data were created through detection of matched molecular pairs and mining bioactivity data in the ChEMBL database. The SwissBioisostere database is hosted by the Swiss Institute of Bioinformatics and available via a web-based interface.

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Figures

Figure 1.
Figure 1.
Overview of the different steps leading to the creation of the SwissBioisostere database.
Figure 2.
Figure 2.
Information on counts of unique replacements stratified by the type of cut that has been performed.
Figure 3.
Figure 3.
Overview about the fragment replacement proposal process. The user enters a chemical substructure in sketcher 1 (1). The query results in an overview page showing all replacements that have been performed for this particular substructure: (2) ΔlogP, ΔtPSA overview that can be used to select subsets, (3) results table, (4) image of performed replacement, which links to a detailed overview page, (5) bioactivity difference distribution, three class classification, (6) sorts columns, (7) data export.
Figure 4.
Figure 4.
Retrieval of details for a particular molecular replacement. The user enters the replacement as chemical substructures in sketcher 1 and 2 (1), or follows a link from the result page presented in Figure 3. The query results in a detailed overview page that presents the underlying data for this particular replacement: (2) general statistics, (3) bioactivity difference distribution plot, (4) bioactivity difference distributions by attachment point context, (5) filter for assay and compound properties, (6) results table, (7) sorts columns, (8) column filter for assays, targets, target classes, (9) detail view for particular data record and (10) data export.
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