2D autocorrelation modelling of the inhibitory activity of cytokinin-derived cyclin-dependent kinase inhibitors

The inhibitory activity towards p34(cdc2)/cyclin b kinase (CBK) enzyme of 30 cytokinin-derived compounds has been successfully modelled using 2D spatial autocorrelation vectors. Predictive linear and non-linear models were obtained by forward stepwise multi-linear regression analysis (MRA) and artificial neural network (ANN) approaches respectively. A variable selection routine that selected relevant non-linear information from the data set was employed prior to networks training. The best ANN with three input variables was able to explain about 87% data variance in comparison with 80% by the linear equation using the same number of descriptors. Similarly, the neural network had higher predictive power. The MRA model showed a linear dependence between the inhibitory activities and the spatial distributions of masses, electronegativities and van der Waals volumes on the inhibitors molecules. Meanwhile, ANN model evidenced the occurrence of non-linear relationships between the inhibitory activity and the mass distribution at different topological distance on the cytokinin-derived compounds. Furthermore, inhibitors were well distributed regarding its activity levels in a Kohonen self-organizing map (SOM) built using the input variables of the best neural network.