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

Residues in the transmembrane region of G protein‐coupled receptors (GPCRs) are important for ligand binding and activation, but the function of individual positions is poorly understood. 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 bioinformatics approaches, such as the evolutionary trace method, entropy–variability plot, and correlated mutation analysis, both qualitatively and quantitatively. Proteins 2006. © 2006 Wiley‐Liss, Inc.