后期促进复合物共激活因子（Cdh1）的结构模型及抑制性化合物的计算机辅助设计
A structural model of the anaphase promoting complex co-activator (Cdh1) and in silico design of inhibitory compounds.
作者信息
Rahimi H, Negahdari B, Shokrgozar M A, Madadkar-Sobhani A, Mahdian R, Foroumadi A, Amin M Kafshdouzi, Karimipoor M
机构信息
Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, I.R. Iran.
Department of Medical Biotechnology, Advanced Medical Science School, Tehran University of Medical Sciences, Tehran, I.R. Iran.
出版信息
Res Pharm Sci. 2015 Jan-Feb;10(1):59-67.
Anaphase promoting complex (APC) controls cell cycle and chromosome segregation. The APC activation occurs after binding of co-activators, cdh1 and cdc20. Cdh1 plays a role in cancer pathogenesis and is known as a potential drug target. The main aim of this study was prediction of 3D structure of cdh1 and designing the inhibitory compounds based on the structural model. First, 3D structure of cdh1 was predicted by means of homology modelling and molecular dynamics tools, MODELLER and Gromacs package, respectively. Then, inhibitory compounds were designed using virtual screening and molecular docking by means AutoDock package. The overall structure of cdh1 is propeller like and each DW40 repeat contains four anti-parallel beta-sheets. Moreover, binding pocket of the inhibitory compounds was determined. The results might be helpful in finding a suitable cdh1 inhibitor for the treatment of cancer.
后期促进复合物（APC）控制细胞周期和染色体分离。APC的激活发生在共激活因子cdh1和cdc20结合之后。Cdh1在癌症发病机制中起作用，并且是已知的潜在药物靶点。本研究的主要目的是预测cdh1的三维结构，并基于该结构模型设计抑制性化合物。首先，分别借助同源建模工具MODELLER和分子动力学工具Gromacs软件包预测cdh1的三维结构。然后，使用AutoDock软件包通过虚拟筛选和分子对接设计抑制性化合物。Cdh1的整体结构呈螺旋桨状，每个DW40重复序列包含四个反平行β折叠。此外，还确定了抑制性化合物的结合口袋。这些结果可能有助于找到一种合适的用于治疗癌症的cdh1抑制剂。
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