title: A structural model of the anaphase promoting complex co-activator (Cdh1) and in silico design of inhibitory compounds.
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.
authors.affiliation: Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, I.R. Iran.
authors.forename: H
authors.initials: H
authors.lastname: Rahimi
authors.affiliation: Department of Medical Biotechnology, Advanced Medical Science School, Tehran University of Medical Sciences, Tehran, I.R. Iran.
authors.forename: B
authors.initials: B
authors.lastname: Negahdari
authors.affiliation: National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, I.R. Iran.
authors.forename: M A
authors.initials: MA
authors.lastname: Shokrgozar
authors.affiliation: Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain ; Department of Bioinformatics, Institute of Biophysics and Biochemistry (IBB), University of Tehran, Tehran, I.R. Iran.
authors.forename: A
authors.initials: A
authors.lastname: Madadkar-Sobhani
authors.affiliation: Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, I.R. Iran.
authors.forename: R
authors.initials: R
authors.lastname: Mahdian
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, I.R. Iran.
authors.forename: A
authors.initials: A
authors.lastname: Foroumadi
authors.affiliation: Faculty of Paramedical Sciences, Qazvin University of Medical Sciences, Qazvin, I.R. Iran.
authors.forename: M Kafshdouzi
authors.initials: MK
authors.lastname: Amin
authors.affiliation: Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, I.R. Iran.
authors.forename: M
authors.initials: M
authors.lastname: Karimipoor
keywords: Cancer; Cdh1; Homology modeling; Virtual screening and docking