A method for the prediction of GPCRs coupling specificity to G-proteins using refined profile Hidden Markov Models |
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Authors: | Nikolaos?G?Sgourakis Pantelis?G?Bagos Panagiotis?K?Papasaikas Email author" target="_blank">Stavros?J?HamodrakasEmail author |
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Institution: | (1) Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Athens, 157 01, Greece |
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Abstract: | Background G- Protein coupled receptors (GPCRs) comprise the largest group of eukaryotic cell surface receptors with great pharmacological
interest. A broad range of native ligands interact and activate GPCRs, leading to signal transduction within cells. Most of
these responses are mediated through the interaction of GPCRs with heterotrimeric GTP-binding proteins (G-proteins). Due to
the information explosion in biological sequence databases, the development of software algorithms that could predict properties
of GPCRs is important. Experimental data reported in the literature suggest that heterotrimeric G-proteins interact with parts
of the activated receptor at the transmembrane helix-intracellular loop interface. Utilizing this information and membrane
topology information, we have developed an intensive exploratory approach to generate a refined library of statistical models
(Hidden Markov Models) that predict the coupling preference of GPCRs to heterotrimeric G-proteins. The method predicts the
coupling preferences of GPCRs to Gs, Gi/o and Gq/11, but not G12/13 subfamilies. |
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