Ligand - based virtual screening procedure for the prediction and the identification of novel β-amyloid aggregation inhibitors using Kohonen maps and Counterpropagation Artificial Neural Networks

In this work we have developed an in silico model to predict the inhibition of β-amyloid aggregation by small organic molecules. In particular we have explored the inhibitory activity of a series of 62 N-phenylanthranilic acids using Kohonen maps and Counterpropagation Artificial Neural Networks. The effects of various structural modifications on biological activity are investigated and novel structures are designed using the developed in silico model. More specifically a search for optimized pharmacophore patterns by insertions, substitutions, and ring fusions of pharmacophoric substituents of the main building block scaffolds is described. The detection of the domain of applicability defines compounds whose estimations can be accepted with confidence.

Graphical abstractIn this work we have developed an in silico model to predict the inhibition of β-amyloid aggregation by small organic molecules. In particular we have explored the inhibitory activity of a series of 62 N-phenylanthranilic acids using Kohonen maps and Counterpropagation Artificial Neural Networks. The effects of various structural modifications on biological activity are investigated and novel structures are designed using the developed in silico model. More specifically a search for optimized pharmacophore patterns by insertions, substitutions, and ring fusions of pharmacophoric substituents of the main building block scaffolds is described. The detection of the domain of applicability defines compounds whose estimations can be accepted with confidence.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► We developed an in silico model to predict the inhibition of β-amyloid aggregation. ► Kohonen maps, Counterpropagation ANN and Decision trees were used as modeling tools. ► A ligand-based virtual screening study was conducted. ► Novel chemistry driven structures within the domain of applicability were proposed.