title: Self-organizing molecular fingerprints: a ligand-based view on drug-like chemical space and off-target prediction.
abstract: BACKGROUND
  Reliable prediction of multiple ligand-receptor interactions for a given bioactive compound helps recognize and understand off-target effects, and enables drug re-purposing and scaffold-hopping in lead discovery. We developed a ligand-based computational method for drug-target prediction that is independent from protein structural analysis.
  
  
  METHODS
  The idea is to infer drug targets from the pharmacophoric feature similarity of known ligands, and define functional target similarity from a ligand perspective, which also provides access to targets with unknown structures. First, known ligands were represented by topological pharmacophoric features. Then, the self-organizing map technique was used to generate fingerprint patterns for similarity analysis, where each resulting fingerprint represents a drug target. Target fingerprints were clustered and analyzed for correlations. Well-structured dendrograms were obtained presenting interpretable and meaningful relationships between drug targets.
  
  
  CONCLUSIONS
  Self-organization of fingerprints reduces noise from molecular pharmacophore descriptors, captures their essential features, and reveals potential cross-activities of ligand classes and off-target effects of bioactive compounds.
authors.affiliation: Johann Wolfgang Goethe-University, Siesmayerstr. 70, D-60323 Frankfurt am Main, Germany. g.schneider@chemie.uni-frankfurt.de
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Tanrikulu
authors.forename: Petra
authors.initials: P
authors.lastname: Schneider
mesh_terms: D016000:Cluster Analysis; D015195:Drug Design; D008024:Ligands; D053858:Metabolic Networks and Pathways; D010447:Peptide Hydrolases / Q000737:chemistry*; D011480:Protease Inhibitors / Q000737:chemistry*; D012984:Software
chemical_list: D008024:Ligands; D011480:Protease Inhibitors; D010447:Peptide Hydrolases