EXPLORATION OF BINDING OF HUMAN GROWTH HORMONE TO ITS RECEPTOR

人生长激素（hGH）以一种非特异性方式与其受体（hGH r）结合。 三体相互作用：一个激素分子和两个相同的 受体的单体形成三聚体。 奇怪的是 三聚体中的受体-受体相互作用是不等价的， 络合物的形成以特定的动力学顺序发生。 我们有 使用形状互补性模拟hGH对hGHR的识别 的三维结构和大分子对接， 探索受体与激素之间可能的结合方式。 的 方法是基于匹配互补形状的战略网站上 分子表面。 我们修改了程序 三体系统 我们发现结合的顺序 实验上也是我们模型的关键。 我们探索了 突变数据可用于hGH以指导我们的模型。 除了 将hGH与hGHR对接，我们进一步测试了我们的方法， 成功地从X射线中复制出16种高分子复合物 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复合物。

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.