title: Predicting mTOR inhibitors with a classifier using recursive partitioning and Naïve Bayesian approaches.
abstract: BACKGROUND
  Mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism, and angiogenesis. Thus, there is a great deal of interest in developing clinical drugs based on mTOR. In this paper, in silico models based on multi-scaffolds were developed to predict mTOR inhibitors or non-inhibitors.
  
  
  METHODS
  First 1,264 diverse compounds were collected and categorized as mTOR inhibitors and non-inhibitors. Two methods, recursive partitioning (RP) and naïve Bayesian (NB), were used to build combinatorial classification models of mTOR inhibitors versus non-inhibitors using physicochemical descriptors, fingerprints, and atom center fragments (ACFs).
  
  
  RESULTS
  A total of 253 models were constructed and the overall predictive accuracies of the best models were more than 90% for both the training set of 964 and the external test set of 300 diverse compounds. The scaffold hopping abilities of the best models were successfully evaluated through predicting 37 new recently published mTOR inhibitors. Compared with the best RP and Bayesian models, the classifier based on ACFs and Bayesian shows comparable or slightly better in performance and scaffold hopping abilities. A web server was developed based on the ACFs and Bayesian method (http://rcdd.sysu.edu.cn/mtor/). This web server can be used to predict whether a compound is an mTOR inhibitor or non-inhibitor online.
  
  
  CONCLUSIONS
  In silico models were constructed to predict mTOR inhibitors using recursive partitioning and naïve Bayesian methods, and a web server (mTOR Predictor) was also developed based on the best model results. Compound prediction or virtual screening can be carried out through our web server. Moreover, the favorable and unfavorable fragments for mTOR inhibitors obtained from Bayesian classifiers will be helpful for lead optimization or the design of new mTOR inhibitors.
authors.affiliation: Research Center for Drug Discovery & Institute of Human Virology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Research Center for Drug Discovery & Institute of Human Virology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Research Center for Drug Discovery & Institute of Human Virology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Research Center for Drug Discovery & Institute of Human Virology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Minghao
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Research Center for Drug Discovery & Institute of Human Virology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Research Center for Drug Discovery & Institute of Human Virology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
mesh_terms: D001499:Bayes Theorem; D008956:Models, Chemical; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D058570:TOR Serine-Threonine Kinases