GPCR-SAS: A web application for statistical analyses on G protein-coupled receptors sequences

G protein-coupled receptors (GPCRs) are one of the largest protein families in mammals. They mediate signal transduction across cell membranes and are important targets for the pharmaceutical industry. The G Protein-Coupled Receptors—Sequence Analysis and Statistics (GPCR-SAS) web application provides a set of tools to perform comparative analysis of sequence positions between receptors, based on a curated structural-informed multiple sequence alignment. The analysis tools include: (i) percentage of occurrence of an amino acid or motif and entropy at a position or range of positions, (ii) covariance of two positions, (iii) correlation between two amino acids in two positions (or two sequence motifs in two ranges of positions), and (iv) snake-plot representation for a specific receptor or for the consensus sequence of a group of selected receptors. The analysis of conservation of residues and motifs across transmembrane (TM) segments may guide the design of more selective ligands or help to rationalize activation mechanisms, among others. As an example, here we analyze the amino acids of the “transmission switch”, that initiates receptor activation following ligand binding. The tool is freely accessible at http://lmc.uab.cat/gpcrsas/.

G蛋白偶联受体（G protein-coupled receptors, GPCRs）是哺乳动物体内最大的蛋白质家族之一，可介导跨细胞膜的信号转导过程，是制药工业的重要靶点。G蛋白偶联受体序列分析与统计（G Protein-Coupled Receptors—Sequence Analysis and Statistics, GPCR-SAS）网页应用，基于经人工注释整理的结构导向多序列比对结果，提供了一系列用于不同受体间序列位点比较分析的工具。其分析工具涵盖：(i) 单个位点或一段位点上的氨基酸或基序（motif）出现频率与熵值；(ii) 两个位点间的协方差；(iii) 两个位点上的两种氨基酸（或两段位点上的两个序列基序）之间的相关性；(iv) 针对特定受体或所选受体组的共有序列的蛇形图（snake-plot）展示。对跨膜（transmembrane, TM）区段内残基与基序的保守性进行分析，可辅助设计选择性更强的配体，或阐释受体激活机制等诸多场景。作为示例，本文对启动配体结合后受体激活过程的“传递开关”氨基酸残基展开了分析。该工具可通过http://lmc.uab.cat/gpcrsas/ 免费访问使用。