title: Identifying enriched drug fragments as possible candidates for metabolic engineering.
abstract: Fragment-based approaches have now become an important component of the drug discovery process. At the same time, pharmaceutical chemists are more often turning to the natural world and its extremely large and diverse collection of natural compounds to discover new leads that can potentially be turned into drugs. In this study we introduce and discuss a computational pipeline to automatically extract statistically overrepresented chemical fragments in therapeutic classes, and search for similar fragments in a large database of natural products. By systematically identifying enriched fragments in therapeutic groups, we are able to extract and focus on few fragments that are likely to be active or structurally important.
  
  
  
  We show that several therapeutic classes (including antibacterial, antineoplastic, and drugs active on the cardiovascular system, among others) have enriched fragments that are also found in many natural compounds. Further, our method is able to detect fragments shared by a drug and a natural product even when the global similarity between the two molecules is generally low.
  
  
  
  A further development of this computational pipeline is to help predict putative therapeutic activities of natural compounds, and to help identify novel leads for drug discovery.
authors: School of Interdisciplinary Informatics, University of Nebraska at Omaha, 1110 South 67th Street, Omaha, 68182, NE, USA.
authors: Sunandini
authors: S
authors: Sharma
authors: School of Interdisciplinary Informatics, University of Nebraska at Omaha, 1110 South 67th Street, Omaha, 68182, NE, USA.
authors: Kritika
authors: K
authors: Karri
authors: School of Interdisciplinary Informatics, University of Nebraska at Omaha, 1110 South 67th Street, Omaha, 68182, NE, USA.
authors: Ishwor
authors: I
authors: Thapa
authors: School of Interdisciplinary Informatics, University of Nebraska at Omaha, 1110 South 67th Street, Omaha, 68182, NE, USA.
authors: Dhundy
authors: D
authors: Bastola
authors: School of Interdisciplinary Informatics, University of Nebraska at Omaha, 1110 South 67th Street, Omaha, 68182, NE, USA. dghersi@unomaha.edu.
authors: Dario
authors: D
authors: Ghersi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry*; D002110:Caffeine / Q000138:chemical synthesis; D062313:Databases, Pharmaceutical; D055808:Drug Discovery / Q000379:methods*; D060847:Metabolic Engineering; D017239:Paclitaxel / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D020058:Styrene / Q000138:chemical synthesis
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; D004364:Pharmaceutical Preparations; D002110:Caffeine; D020058:Styrene; D017239:Paclitaxel
keywords: Chemoinformatics; Metabolic engineering; Natural products; Small molecules