Use of amino acid composition to predict ligand-binding sites
Use of amino acid composition to predict ligand-binding sites
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DOI：
10.1021/ci6002202
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发表时间：
2007-03-01
影响因子：
5.6
通讯作者：
Hirayama, Noriaki
中科院分区：
文献类型：
--
作者：
Soga, Shinji;Shirai, Hiroki;Hirayama, Noriaki
基于X射线分析确定的配体-蛋白质复合物配体结合位点上的特定氨基酸组成，提出了一种预测类药物化合物在蛋白质表面结合位点的新方法。一个配置文件，代表的20个标准的氨基酸中的每一个在类药物分子的结合位点的偏好，获得了一个小的一组高品质的复杂结构。从这些配置文件中创建了一个称为配体结合倾向（PLB）的指数。PLB指数用于预测804配体在其结构通过X射线分析确定的蛋白质上的所有潜在结合位点处的结合倾向。如果把首两个最高的公共小巴指数的地盘计算在内，成功预测的地盘所占的百分比高达86。PLB预测相对简单，但验证研究表明，它可以快速准确地检测配体结合位点，特别是类药物分子的结合位点。因此，PLB指数可用于预测未表征蛋白质结构的配体结合位点，也可用于识别已知药物靶点的新药物结合位点。
A novel method for predicting the binding sites for druglike compounds on the surface of proteins was developed on the basis of the specific amino acid composition observed at the ligand-binding sites of ligand-protein complexes determined by X-ray analysis. A profile representing the preference of each of the 20 standard amino acids at the binding sites of druglike molecules was obtained for a small set of high-quality complex structures. An index termed propensity for ligand binding (PLB) was created from these profiles. The PLB index was used to predict the propensity of binding for 804 ligands at all potential binding sites on the proteins whose structures were determined by X-ray analysis. If the sites with the first two highest PLB indices are taken into consideration, the successfully predicted sites reached a high percentage of 86. The PLB prediction is relatively simple, but the validation study showed that it is both fast and accurate to detect ligand-binding sites, especially the binding sites of druglike molecules. Therefore, the PLB index can be used to predict the ligand-binding sites of uncharacterized protein structures and also to identify novel drug-binding sites of known drug targets.