title: Connecting proteins with drug-like compounds: Open source drug discovery workflows with BindingDB and KNIME.
abstract: Today's large, public databases of protein-small molecule interaction data are creating important new opportunities for data mining and integration. At the same time, new graphical user interface-based workflow tools offer facile alternatives to custom scripting for informatics and data analysis. Here, we illustrate how the large protein-ligand database BindingDB may be incorporated into KNIME workflows as a step toward the integration of pharmacological data with broader biomolecular analyses. Thus, we describe a collection of KNIME workflows that access BindingDB data via RESTful webservices and, for more intensive queries, via a local distillation of the full BindingDB dataset. We focus in particular on the KNIME implementation of knowledge-based tools to generate informed hypotheses regarding protein targets of bioactive compounds, based on notions of chemical similarity. A number of variants of this basic approach are tested for seven existing drugs with relatively ill-defined therapeutic targets, leading to replication of some previously confirmed results and discovery of new, high-quality hits. Implications for future development are discussed. Database URL: www.bindingdb.org.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA, mgilson@ucsd.edu.
authors.forename: George
authors.initials: G
authors.lastname: Nicola
authors.affiliation: Department of Computer and Information Science, Konstanz University, 78457 Konstanz, Germany, and.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Berthold
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hedrick
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA, mgilson@ucsd.edu.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Gilson
mesh_terms: D000818:Animals; D055808:Drug Discovery; D004347:Drug Interactions; D006801:Humans; D051188:Knowledge Bases; D004364:Pharmaceutical Preparations; D010599:Pharmacokinetics; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations; D011506:Proteins