A naive Bayes model to predict coupling between seven transmembrane domain receptors and G-proteins.
BACKGROUND
An understanding of the coupling between a G-protein coupled receptor (GPCR) and a specific class of heterotrimeric GTP-binding proteins (G-proteins) is vital for further comprehending the function of the receptor within a cell. However, predicting G-protein coupling based on the amino acid sequence of a receptor has been a daunting task. While experimental data for G-protein coupling exist, published models that rely on sequence based prediction are few. In this study, we have developed a Naive Bayes model to successfully predict G-protein coupling specificity by training over 80 GPCRs with known coupling. Each intracellular domain of GPCRs was treated as a discrete random variable, conditionally independent of one another. In order to determine the conditional probability distributions of these variables, ClustalW-generated phylogenetic trees were used as an approximation for the clustering of the intracellular domain sequences. The sampling of an intracellular domain sequence was achieved by identifying the cluster containing the homologue with the highest sequence similarity.


RESULTS
Out of 55 GPCRs validated, the model yielded a correct classification rate of 72%. Our model also predicted multiple G-protein coupling for most of the GPCRs in the validation set. The Bayesian approach in this work offers an alternative to the experimental approach in order to answer the biological problem of GPCR/G-protein coupling selectivity.


BACKGROUND
Academic users should send their request for the perl program for calculating likelihood probabilities at jack.cao@astrazeneca.com.


BACKGROUND
The materials can be viewed at http://www.astrazeneca-montreal.com/AZRDM_info/supporting_info.pdf.
Cao
Jack
J
Department of Molecular Sciences, AstraZeneca R&D Montreal, 7171 Frederick-Banting Street, St-Laurent, Quebec H4S 1Z9, Canada. jack.cao@astrazeneca.com
Panetta
Rosemarie
R
Yue
Shiyi
S
Steyaert
Alain
A
Young-Bellido
Michele
M
Ahmad
Sultan
S
D000465:Algorithms; D000595:Amino Acid Sequence; D001499:Bayes Theorem; D001665:Binding Sites; D016000:Cluster Analysis; D030562:Databases, Protein; D005240:Feasibility Studies; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008956:Models, Chemical; D008957:Models, Genetic; D015233:Models, Statistical; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D010363:Pattern Recognition, Automated; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid
D009479:Neuropeptides; D019204:GTP-Binding Proteins