title: Automatic design of decision-tree induction algorithms tailored to flexible-receptor docking data.
abstract: BACKGROUND
  This paper addresses the prediction of the free energy of binding of a drug candidate with enzyme InhA associated with Mycobacterium tuberculosis. This problem is found within rational drug design, where interactions between drug candidates and target proteins are verified through molecular docking simulations. In this application, it is important not only to correctly predict the free energy of binding, but also to provide a comprehensible model that could be validated by a domain specialist. Decision-tree induction algorithms have been successfully used in drug-design related applications, specially considering that decision trees are simple to understand, interpret, and validate. There are several decision-tree induction algorithms available for general-use, but each one has a bias that makes it more suitable for a particular data distribution. In this article, we propose and investigate the automatic design of decision-tree induction algorithms tailored to particular drug-enzyme binding data sets. We investigate the performance of our new method for evaluating binding conformations of different drug candidates to InhA, and we analyze our findings with respect to decision tree accuracy, comprehensibility, and biological relevance.
  
  
  RESULTS
  The empirical analysis indicates that our method is capable of automatically generating decision-tree induction algorithms that significantly outperform the traditional C4.5 algorithm with respect to both accuracy and comprehensibility. In addition, we provide the biological interpretation of the rules generated by our approach, reinforcing the importance of comprehensible predictive models in this particular bioinformatics application.
  
  
  CONCLUSIONS
  We conclude that automatically designing a decision-tree algorithm tailored to molecular docking data is a promising alternative for the prediction of the free energy from the binding of a drug candidate with a flexible-receptor.
authors.affiliation: University of São Paulo, São Carlos, Brazil. rcbarros@icmc.usp.br
authors.forename: Rodrigo C
authors.initials: RC
authors.lastname: Barros
authors.forename: Ana T
authors.initials: AT
authors.lastname: Winck
authors.forename: Karina S
authors.initials: KS
authors.lastname: Machado
authors.forename: Márcio P
authors.initials: MP
authors.lastname: Basgalupp
authors.forename: André C P L F
authors.initials: AC
authors.lastname: de Carvalho
authors.forename: Duncan D
authors.initials: DD
authors.lastname: Ruiz
authors.forename: Osmar Norberto
authors.initials: ON
authors.lastname: de Souza
mesh_terms: D000465:Algorithms; D000995:Antitubercular Agents / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D019295:Computational Biology; D003663:Decision Trees; D019020:Directed Molecular Evolution; D015195:Drug Design; D019277:Entropy; D008024:Ligands; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010088:Oxidoreductases / Q000737:chemistry*; D011485:Protein Binding
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D008024:Ligands; D010088:Oxidoreductases; C085257:InhA protein, Mycobacterium