Ye Kai, Lameijer Eric-Wubbo M, Beukers Margot W, Ijzerman Adriaan P
Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
Proteins. 2006 Jun 1;63(4):1018-30. doi: 10.1002/prot.20899.
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.
G蛋白偶联受体（GPCRs）跨膜区域的残基对于配体结合和激活很重要，但各个位置的功能却了解甚少。通过对A类GPCRs（按亚家族分组）进行序列比对，我们提出了一种所谓的“双熵分析”方法，以确定A类GPCRs跨膜区域中各个位置的潜在作用。在我们的方法中，这些位置看起来是分散的，但根据其生物学功能在很大程度上聚集在一起。与其他生物信息学方法（如进化追踪法、熵-变异性图和相关突变分析）相比，我们的方法在定性和定量方面都显得更优越。
