TOPK是治疗癌症的一个新的蛋白质靶标，它构成的复合体结构及其调控癌细胞凋亡的分子物理机制是一个亟待解决的科学问题。本项目拟对几个关键TOPK复合体进行研究，分别解析TOPK与蛋白质CDKl／CyclinB、c-Raf、As2O3构成的复合体的三维原子构象，研究它们之间的绑定相互作用，认证关键作用位点，揭示其激活TOPK的分子物理机制，探索调制其活性的新位点。研究TOPK分别与hDlg、p53、p57、H2AX的复合体原子结构，讨论它们之间绑定相互作用特性，确定绑定界面和结合位点，揭示其调节癌细胞的增值和凋亡的分子物理机理，探寻新型调控癌的新靶点。分析TOPK与其抑制剂对接的原子空间构象，揭示其抑制TOPK活性的机制。在获得上述位点和靶点的基础上，筛选新型TOPK抑制剂。该研究不但对揭示癌症的分子物理机制具有重要的学术意义，而且对研发新型癌症治疗药物具有实际的理论指导意义。

TOPK is a new melecular target for the therapy of cancer. Its complex structure and the mechanism of regulating the apoptosis of cancer cells is a scientific problem to be solved urgently. In this study, we focus the several key TOPK complexes. The three-dimensional atomic conformation of TOPK and cdkl / cyclin B, c-Raf, As2O3 will be analyzed respectively. We will investigate the interaction of them and identify the key site to reveal the molecular mechanism of TOPK activation. And the new activating sites will be searched tentatively. We will study the complex structure of TOPK with hDlg, p53, p57, H2AX, respectively, to determine their coupling surface and binding site, and to explore the mechanism of regulating the division and apoptosis of cancer cells, and search the new targets regulating cancer. The mechanism of the inhibition of TOPK activity will be revealed by analyzing the atomic space conformation of TOPK and its inhibitors. On this basis of the sites and targets, the new TOPK inhibitors will be screened virtually. This study is not only important academic significance to reveal the molecular mechanism of cancer, but also is ppratically theoretical significance for the development of new cancer drugs.