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Multi-space classification for predicting GPCR-ligands

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Summary

A classification of molecules depends on the descriptor set which is used to represent the compounds, and each descriptor could be regarded as one perception of a molecule. In this study we show that a combination of several classifiers that are grounded on separate descriptor sets can be superior to a single classifier that was built using all available descriptors. The task of predicting ligands of G-protein coupled receptors (GPCR) served as an example application. The perceptron, multilayer neural networks, and radial basis function (RBF) networks were employed for prediction. We developed classifiers with and without descriptor selection. Prediction accuracy was assessed by the area under the receiver operating characteristic (ROC) curve. In the case with descriptor selection both the selection and the rank order of the descriptors depended on the type and topology of the neural networks. We demonstrate that the overall prediction accuracy of the system can be improved by joining neural network classifiers of different type and topology using a “jury network” that is trained to evaluate the predictions from the individual classifiers. Seventy-one percent correct prediction of GPCR ligands was obtained.

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Abbreviations

BP:

backpropagation algorithm

GA:

genetic algorithm

HTS:

high-throughput screening

MLP:

multilayer neural network (multilayer perceptron)

MSE:

mean square error

QSAR:

quantitative structure–activity relationship

RBF:

radial basis function

ROC:

receiver operating characteristic curve

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Authors and Affiliations

  1. Institut für Organische Chemie und Chemische Biologie, Johann Wolfgang Goethe-Universität, Marie-Curie-Strasse 11, D-60439, Frankfurt, Germany

    Alireza Givehchi & Gisbert Schneider

  2. Klinik und Poliklinik für Neurochirurgie, Klinik und Poliklinik für Neurologie, Universitätsklinikum Münster, Albert-Schweitzer-Strasse 33, D-48129, Münster, Germany

    Alireza Givehchi

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  1. Alireza Givehchi
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  2. Gisbert Schneider
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Correspondence to Alireza Givehchi.

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Givehchi, A., Schneider, G. Multi-space classification for predicting GPCR-ligands. Mol Divers 9, 371–383 (2005). https://doi.org/10.1007/s11030-005-6293-4

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