Modeling of binding modes and inhibition mechanism of some natural ligands of farnesyl transferase using molecular docking.
Modeling of binding modes and inhibition mechanism of some natural ligands of farnesyl transferase using molecular docking.
复制标题
DOI：
10.1021/jm011075w
复制
发表时间：
2002-02
影响因子：
7.3
通讯作者：
A. Pedretti;L. Villa;G. Vistoli
中科院分区：
文献类型：
--
作者：
A. Pedretti;L. Villa;G. Vistoli
文献中已经报道了几种法呢基转移酶的天然抑制剂：一些化合物与法呢基焦磷酸（FPP）竞争，而另一些化合物与Ras蛋白竞争，尽管通常很难强调它们的抑制机制，这对于几种天然化合物来说仍然是未知的。这项工作的目的是表明分子对接分析可以成功地用于强调这些天然化合物的抑制机制。首先，通过 BioDock（该程序能够揭示每个配体最可能的结合模式）对选定的化合物进行详细的对接分析。通过将这些结果与先前确定的天然底物的结合位点进行比较，可以突出所选化合物的位点特异性和抑制机制。此外，还可以将这些分子的结合模式与其脂极值联系起来，肽模拟物的脂极值明显低于 FPP 模拟物，并揭示了预测和理解这些天然衍生物的抑制机制的直接方法。
Several natural inhibitors of farnesyl transferase have been reported in the literature: some compounds are competitive with farnesyl pyrophosphate (FPP), whereas other ones are competitive with Ras proteins, even though it is usually hard to highlight their inhibition mechanism, which is still unknown for several natural compounds. The aim of this work is to show that the molecular docking analysis can be successfully used to underline the inhibition mechanism of these natural compounds. First, the selected compounds were subjected to a detailed docking analysis, by means of BioDock, a program able to reveal the most likely binding mode for each ligand. By comparing these results with the binding sites for the natural substrates, earlier determined, it was possible to highlight the site specificity and the inhibition mechanism of the selected compounds. In addition, it is possible to relate the binding mode of these molecules with their lipole values, which is appreciably less for peptidomimetics than for FPP mimetic and reveals a straightforward method to predict and to understand the inhibition mechanism of these natural derivatives.