An efficient piecewise linear model for predicting activity of caspase-3 inhibitors

Abstract

Background and purpose of the studyMultimodal distribution of descriptors makes it more difficult to fit a single global model to model the entire data set in quantitative structure activity relationship (QSAR) studies.MethodsThe linear (Multiple linear regression; MLR), non-linear (Artificial neural network; ANN), and an approach based on “Extended Classifier System in Function approximation” (XCSF) were applied herein to model the biological activity of 658 caspase-3 inhibitors.ResultsVarious kinds of molecular descriptors were calculated to represent the molecular structures of the compounds. The original data set was partitioned into the training and test sets by the K-means classification method. Prediction error on the test data set indicated that the XCSF as a local model estimates caspase-3 inhibition activity, better than the global models such as MLR and ANN. The atom-centered fragment type CR2X2, electronegativity, polarizability, and atomic radius and also the lipophilicity of the molecule, were the main independent factors contributing to the caspase-3 inhibition activity.ConclusionsThe results of this study may be exploited for further design of novel caspase-3 inhibitors.

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In Silico Studies in Drug Research Against Neurodegenerative Diseases

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Efficient synthesis, biological evaluation, and docking study of isatin based derivatives as caspase inhibitors

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