title: Virtual affinity fingerprints for target fishing: a new application of Drug Profile Matching.
abstract: We recently introduced Drug Profile Matching (DPM), a novel virtual affinity fingerprinting bioactivity prediction method. DPM is based on the docking profiles of ca. 1200 FDA-approved small-molecule drugs against a set of nontarget proteins and creates bioactivity predictions based on this pattern. The effectiveness of this approach was previously demonstrated for therapeutic effect prediction of drug molecules. In the current work, we investigated the applicability of DPM for target fishing, i.e. for the prediction of biological targets for compounds. Predictions were made for 77 targets, and their accuracy was measured by Receiver Operating Characteristic (ROC) analysis. Robustness was tested by a rigorous 10-fold cross-validation procedure. This procedure identified targets (N = 45) with high reliability based on DPM performance. These 45 categories were used in a subsequent study which aimed at predicting the off-target profiles of currently approved FDA drugs. In this data set, 79% of the known drug-target interactions were correctly predicted by DPM, and additionally 1074 new drug-target interactions were suggested. We focused our further investigation on the suggested interactions of antipsychotic molecules and confirmed several interactions by a review of the literature.
authors.affiliation: Department of Biochemistry, Institute of Biology, Eötvös Loránd University, Pázmány Péter sétány 1/C, H-1117 Budapest, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Peragovics
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Simon
authors.forename: László
authors.initials: L
authors.lastname: Tombor
authors.forename: Balázs
authors.initials: B
authors.lastname: Jelinek
authors.forename: Péter
authors.initials: P
authors.lastname: Hári
authors.forename: Pál
authors.initials: P
authors.lastname: Czobor
authors.forename: András
authors.initials: A
authors.lastname: Málnási-Csizmadia
mesh_terms: D014150:Antipsychotic Agents / Q000378:metabolism / Q000494:pharmacology; D062313:Databases, Pharmaceutical; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011336:Probability; D011485:Protein Binding; D012372:ROC Curve; D015203:Reproducibility of Results; D014584:User-Computer Interface
chemical_list: D014150:Antipsychotic Agents; D004364:Pharmaceutical Preparations