title: In silico site of metabolism prediction for human UGT-catalyzed reactions.
abstract: BACKGROUND
  The human uridine diphosphate-glucuronosyltransferase enzyme family catalyzes the glucuronidation of the glycosyl group of a nucleotide sugar to an acceptor compound (substrate), which is the most common conjugation pathway that serves to protect the organism from the potential toxicity of xenobiotics. Moreover, it could affect the pharmacological profile of a drug. Therefore, it is important to identify the metabolically labile sites for glucuronidation.
  
  
  RESULTS
  In the present study, we developed four in silico models to predict sites of glucuronidation, for four major sites of metabolism functional groups, i.e. aliphatic hydroxyl, aromatic hydroxyl, carboxylic acid or amino nitrogen, respectively. According to the mechanism of glucuronidation, a series of 'local' and 'global' molecular descriptors characterizing the atomic reactivity, bonding strength and physical-chemical properties were calculated and selected with a genetic algorithm-based feature selection approach. The constructed support vector machine classification models show good prediction performance, with the balanced accuracy ranging from 0.88 to 0.96 on test set. For further validation, our models can successfully identify 84% of experimentally observed sites of metabolisms for an external test set containing 54 molecules.
  
  
  METHODS
  The software somugt based on our models is available at www.dddc.ac.cn/adme/jlpeng/somugt_win32.zip.
authors.affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China and School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Peng
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.forename: Qiancheng
authors.initials: Q
authors.lastname: Shen
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zheng
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Luo
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Kaixian
authors.initials: K
authors.lastname: Chen
mesh_terms: D055162:Biocatalysis; D003198:Computer Simulation; D014453:Glucuronosyltransferase / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D060388:Support Vector Machine
chemical_list: D014453:Glucuronosyltransferase