A two-entropies analysis to identify functional positions in the transmembrane region of class A G protein-coupled receptors.

Residues in the transmembrane re- gion of G protein-coupled receptors (GPCRs) are important for ligand binding and activation, but the function of individual positions is poorly under- stood. Using a sequence alignment of class A GPCRs (grouped in subfamilies), we propose a so-called "two-entropies analysis" to determine the potential role of individual positions in the transmembrane region of class A GPCRs. In our approach, such positions appear scattered, while largely clustered according to their biological function. Our method appears superior when compared to other bioinfor- matics approaches, such as the evolutionary trace method, entropy-variability plot, and correlated mu- tation analysis, both qualitatively and quantita- tively. Proteins 2006;63:1018 -1030.