A structural model of the anaphase promoting complex co-activator (Cdh1) and in silico design of inhibitory compounds

H Rahimi, B Negahdari, MA Shokrgozar, A Madadkar-Sobhani, R Mahdian, A Foroumadi, M Kafshdouzi Amin, M Karimipoor

Abstract


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.


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