Gallet X, Charloteaux B, Thomas A, Brasseur R
Centre de Biophysique Moléculaire Numérique, Faculté Agronomique, Gembloux, 5030, Belgium.
J Mol Biol. 2000 Sep 29;302(4):917-26. doi: 10.1006/jmbi.2000.4092.
A simple method for predicting residues involved in protein interaction sites is proposed. In the absence of any structural report, the procedure identifies linear stretches of sequences as "receptor-binding domains" (RBDs) by analysing hydrophobicity distribution. The sequences of two databases of non-homologous interaction sites eliciting various biological activities were tested; 59-80 % were detected as RBDs. A statistical analysis of amino acid frequencies was carried out in known interaction sites and in predicted RBDs. RBDs were predicted from the 80,000 sequences of the Swissprot database. In both cases, arginine is the most frequently occurring residue. The RBD procedure can also detect residues involved in specific interaction sites such as the DNA-binding (95 % detected) and Ca-binding domains (83 % detected). We report two recent analyses; from the prediction of RBDs in sequences to the experimental demonstration of the functional activities. The examples concern a retroviral Gag protein and a penicillin-binding protein. We support that this method is a quick way to predict protein interaction sites from sequences and is helpful for guiding experiments such as site-specific mutageneses, two-hybrid systems or the synthesis of inhibitors.
本文提出了一种预测蛋白质相互作用位点中涉及残基的简单方法。在没有任何结构报告的情况下，该程序通过分析疏水性分布将序列的线性片段识别为“受体结合域”（RBDs）。对两个引发各种生物活性的非同源相互作用位点数据库的序列进行了测试；59 - 80%被检测为RBDs。在已知的相互作用位点和预测的RBDs中对氨基酸频率进行了统计分析。从Swissprot数据库的80,000个序列中预测了RBDs。在这两种情况下，精氨酸都是最常出现的残基。RBD程序还可以检测参与特定相互作用位点的残基，如DNA结合域（95%被检测到）和钙结合域（83%被检测到）。我们报告了两项最新分析；从序列中RBDs的预测到功能活性的实验证明。实例涉及一种逆转录病毒Gag蛋白和一种青霉素结合蛋白。我们支持这种方法是从序列预测蛋白质相互作用位点的快速途径，有助于指导诸如位点特异性诱变、双杂交系统或抑制剂合成等实验。
