title: Modeling of activity of cyclic urea HIV-1 protease inhibitors using regularized-artificial neural networks.
abstract: Artificial neural networks (ANNs) were used to model both inhibition of HIV-1 protease (K(i)) and inhibition of HIV replication (IC90) for 55 cyclic urea derivatives using constitutional and 2D descriptors. As a preliminary step, linear dependences were established by multiple linear regression (MLR) approaches, selecting the relevant descriptors by genetic algorithm (GA) feature selection. For ANN models non-linear GA feature selection was also applied. Non-linear modeling of K(i) overcame the results of the linear one using four properties, keeping in mind standard Pearson R correlation coefficients (0.931 vs. 0.862) and leave one out (LOO) cross-validation analysis (Q(LOO)2 = 0.703 vs. 0.510). On the other hand, IC90 modeling was insoluble by a linear approach: no predictive model was achieved; however, a non-linear relation was encountered according to statistic results (R = 0.891; Q(LOO)2 = 0.568). The best non-linear models suggested the influence of the presence of nitrogen atoms and the molecular volume distribution in the inhibitor structures on the HIV-1 protease inhibition as well as that the inhibition of HIV replication was dependent on the occurrence of five-member rings. Finally, inhibitors were well distributed regarding its activity levels in a Kohonen self-organizing map built using the input variables of the best non-linear models.
authors.affiliation: Molecular Modeling Group, Center for Biotechnological Studies, University of Matanzas, Matanzas, Cuba.
authors.forename: Michael
authors.initials: M
authors.lastname: Fernández
authors.forename: Julio
authors.initials: J
authors.lastname: Caballero
mesh_terms: D000465:Algorithms; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1; D016014:Linear Models; D016571:Neural Networks, Computer; D014508:Urea / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D017320:HIV Protease Inhibitors; D014508:Urea