EXPLORATION OF BINDING OF HUMAN GROWTH HORMONE TO ITS RECEPTOR

人生长激素(HGH)与其受体(HGHr)结合 三体相互作用：一个荷尔蒙分子和两个相同的分子 受体的单体形成一个三聚体。奇怪的是， 三聚体中激素与受体的相互作用不是等价的， 络合物的形成按特定的动力学顺序进行。我们有 利用形状互补模拟hGH对hGHr的识别 三维结构和大分子对接到 探索受体和激素之间可能的结合模式。这个 方法的基础是匹配互补形状的战略站点 分子表面。我们修改了程序以检查 三体系统。我们发现，我们看到的结合顺序 实验对我们的模型也是必不可少的。我们探索了如何使用 HGH的突变数据可用于指导我们的模型。除了……之外 将hGH对接到hGHR，我们通过以下方式进一步测试了我们的方法 从X射线中成功地再现了16个大分子络合物 晶体结构，包括酶抑制剂，抗体-抗原， 蛋白质二聚体和蛋白质-DNA复合体。

Human growth hormone (hGH) binds to its receptor (hGHr) in a three-body interaction: one molecule of the hormone and two identical monomers of the receptor form a trimer. Curiously, the hormone-receptor interactions in the trimer are not equivalent and the formation of the complex occurs in a specific kinetic order. We have modeled the recognition of hGH to the hGHr using shape complementarity of the three-dimensional structures and macromolecular docking to explore possible binding modes between the receptor and hormone. The method is based upon matching complementary-shaped strategic sites on the molecular surface. We modified the procedure to examine three-body systems. We found that the order of binding seen experimentally is also essential to our model. We explored the use of mutational data available for hGH to guide our model. In addition to docking hGH to the hGHr, we further tested our methodology by successfully reproducing sixteen macromolecular complexes from X-ray crystal structures, including enzyme-inhibitor, antibody-antigen, protein dimer and protein-DNA complexes.