Prediction of the coupling specificity of GPCRs to four families of G-proteins using hidden Markov models and artificial neural networks.
BACKGROUND
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 G(i/o), G(q/11) and G(s), not including G(12/13)-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 G(12/13), whereas unlike other methods avoids overpredictions (false positives) when non-GPCR sequences are encountered.


BACKGROUND
A webserver for academic users is available at http://bioinformatics.biol.uoa.gr/PRED-COUPLE2
Sgourakis
Nikolaos G
NG
Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Greece.
Bagos
Pantelis G
PG
Hamodrakas
Stavros J
SJ
D000818:Animals; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D003201:Computers; D030541:Databases, Genetic; D005189:False Positive Reactions; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics*; D015723:Gene Library; D017343:Genes, Plant; D006801:Humans; D008024:Ligands; D008390:Markov Chains; D008954:Models, Biological; D016571:Neural Networks, Computer; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015203:Reproducibility of Results; D012984:Software
D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019205:GTP-Binding Protein alpha Subunits, Gs