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Bioinformatics Advance Access originally published online on September 20, 2005
Bioinformatics 2005 21(22):4101-4106; doi:10.1093/bioinformatics/bti679
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions{at}oxfordjournals.org

Prediction of the coupling specificity of GPCRs to four families of G-proteins using hidden Markov models and artificial neural networks

Nikolaos G. Sgourakis , Pantelis G. Bagos and Stavros J. Hamodrakas *

Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens Athens 157 01, Greece

*To whom correspondence should be addressed.

Motivation: G-protein coupled receptors are a major class of eukaryotic cell-surface receptors. A very important aspect of their function is the specific interaction (coupling) with members of four G-protein families. A single GPCR may interact with members of more than one G-protein families (promiscuous coupling). To date all published methods that predict the coupling specificity of GPCRs are restricted to three main coupling groups Gi/o, Gq/11 and Gs, not including G12/13-coupled or other promiscuous receptors.

Results: We present a method that combines hidden Markov models and a feed-forward artificial neural network to overcome these limitations, while producing the most accurate predictions currently available. Using an up-to-date curated dataset, our method yields a 94% correct classification rate in a 5-fold cross-validation test. The method predicts also promiscuous coupling preferences, including coupling to G12/13, whereas unlike other methods avoids overpredictions (false positives) when non-GPCR sequences are encountered.

Availability: A webserver for academic users is available at http://bioinformatics.biol.uoa.gr/PRED-COUPLE2

Contact: shamodr{at}cc.uoa.gr

Supplementary information: Results for promiscuous receptors can be found at: http://bioinformatics.biol.uoa.gr/PRED-COUPLE2/tables

Received on August 16, 2005; revised on September 12, 2005; accepted on September 12, 2005

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