Automatic design of decision-tree induction algorithms tailored to flexible-receptor docking data

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.

Herbicides in the upper Poxim River, Sergipe, and the risk of contamination of water resources

Increased agricultural activity in watershed areas has been causing concern over contamination by herbicides in agricultural areas. The problem becomes more important when contamination can affect water for human consumption, as happens with water from the Poxim river, which supplies the city of Aracaju, capital of the State of Sergipe. The aim of this study was to evaluate the risk of contamination by herbicides to both surface and groundwater in the upper sub-basin of the Poxim River, and to detect the presence of the active ingredients Diuron and Ametrine up-river from the sugar-cane plantations. Risk analysis was carried out using criteria from the Environmental Protection Agency (EPA), the GUS index, and the GOSS method. It was observed that several active ingredients are at risk of leaching, demonstrating the importance of monitoring the river to control both the quality of water and the frequency and volume of herbicides used in the region. Based on the results, monitoring was carried out bi-monthly from July 2009 to July 2010 at two sampling points. Water samples were analyzed in the laboratory, where the presence of Diuron and Ametrine was noted. Water quality in the Sub-basin of the Rio Poxim is being influenced by the use of herbicides in the region. There was an increase in herbicide concentration in the surface water during the rainy season, possibly caused by soil runoff.

Reversible polymerization of novel monomers bearing furan and plant oil moieties: a double click exploitation of renewable resources

Monomers based on plant oil derivatives bearing furan heterocycles appended through thiol-ene click chemistry were prepared and, subsequently, polymerized via a second type of click reaction, i. e. the Diels-Alder (DA) polycondensation between furan and maleimide complementary moieties. Two basic approaches were considered for these DA polymerizations, namely (i) the use of monomers with two terminal furan rings in conjunction with bismaleimides (AA + BB systems) and (ii) the use of a protected AB monomer incorporating both furan and maleimide end groups. This study clearly showed that both strategies were successful, albeit with different outcomes, in terms of the nature of the ensuing products. The application of the retro-DA reaction to these polymers confirmed their thermoreversible character, i. e. the clean-cut return to their respective starting monomers, opening the way to original macromolecular materials with interesting applications, like mendability and recyclability.