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QSAR Study of the Inhibitors of the Acetyl-CoA Carboxylase 1 and 2 using Bayesian Regularized Genetic Neural Networks: A Comparative Study

posted on 05.12.2017, 10:06 by Abolfazl Valadkhani, Mohammad Asadollahi-Baboli, Ahmad Mani-Varnosfaderani

Linear and non-linear quantitative structure-activity relationship (QSAR) models were presented for modeling and predicting anti-diabetic activities of a set of inhibitors of acetyl-CoA carboxylase 1 and 2 (ACC1 and ACC2). Different algorithms were utilized to choose the best variables among large numbers of descriptors and then these selected descriptors were used for non-linear (artificial neural network) and linear (multiple linear regression) modeling. The variable selection methods were consisted of stepwise-multiple linear regression (stepwise-MLR), successive projections algorithm (SPA), genetic algorithm-multiple linear regression (GA-MLR) and Bayesian regularized genetic neural networks (BRGNNs). The prediction abilities of the models were evaluated by Monte Carlo cross validation (MCCV) in variable selection and modeling steps. The results revealed that the best variables for describing the inhibition mechanism of ACC were among topological charge indices, radial distribution function, geometrical, and autocorrelation descriptors. The statistical parameters of R2 and root mean square error (RMSE) indicated that BRGNNs is superior for modeling the inhibitory activity of ACC modulators over the other methods. The sensitivity analysis together with the frequency of the selected molecular descriptors in this work can establish an understanding to the mechanism of ACC inhibitory activity of small molecules.