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

Bioinformatics. 2005 Nov 15;21(22):4101-6. doi: 10.1093/bioinformatics/bti679. Epub 2005 Sep 20.

Abstract

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 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.

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

MeSH terms

  • Animals
  • Computational Biology / methods*
  • Computer Simulation
  • Computers
  • Databases, Genetic
  • False Positive Reactions
  • GTP-Binding Protein alpha Subunits, G12-G13 / genetics
  • GTP-Binding Protein alpha Subunits, Gi-Go / genetics
  • GTP-Binding Protein alpha Subunits, Gq-G11 / genetics
  • GTP-Binding Protein alpha Subunits, Gs / genetics
  • GTP-Binding Proteins / genetics*
  • Gene Library
  • Genes, Plant
  • Humans
  • Ligands
  • Markov Chains
  • Models, Biological
  • Neural Networks, Computer*
  • Protein Binding
  • Receptors, G-Protein-Coupled / metabolism*
  • Reproducibility of Results
  • Software

Substances

  • Ligands
  • Receptors, G-Protein-Coupled
  • GTP-Binding Proteins
  • GTP-Binding Protein alpha Subunits, G12-G13
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • GTP-Binding Protein alpha Subunits, Gs