鸟嘌呤核糖开关识别配体小分子

Computational Studies of the Binding of Ligands to the Guanine Riboswitch Aptamer

鸟嘌呤核糖开关是一类位于mRNA的非翻译区,可直接结合有机代谢物,通过调整自身构象变化从而调控基因表达的mRNA元件.鸟嘌呤核糖开关识别配体具有高度特异性和选择性.用动力学模拟的方法,研究鸟嘌呤核糖开关特异识别配体小分子的本质和用热力学积分算法计算核糖开关与配体分子的相对结合自由能.研究发现,核糖开关的结合口袋与配体通过氢键形式相互作用,不同配体与核糖开关结合的亲和力不同.嘌呤配体2-号位对核糖开关的结合必不可少,6-号位对核糖开关的结合关系复杂.

The Guanine Riboswitch is genetic regulatory element found in the non translation region located of mRNA. It can be directly combined with organic metabolites to induces conformational changes to control gene expression. Recognition of them has highly specificity and selectivity. In this work, we studied the nature of the Guanine Riboswitch and ligands by molecular dynamics simulation. Then, the calcu lation of the relative binding free energy of them by Thermodynamic Integration. The study found that the binding pocket of Riboswitch form Waston-Crick base pairs with ligand and we learned that the affinities are different when the binding of different ligands to Riboswitch. These data indicate a more complicated relationship between the 6-position of 1he ligand and the RNA and The 2-position of the purine ligand is essential for the recognition. As an ideal target of new drugs, the Guanine Riboswitch has an important role in the design and development of new drugs.