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Identification of potent inhibitors for chromodomain-helicase- DNA-binding protein 1-like through moleculardocking studies

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Abstract

Chromodomain-helicase-DNA-binding protein 1-like is a chromodomain-containing protein in the SNF2-like family of ATPases. It has the capability to sustain proliferation in cell, encourage tumor growth and prevent apoptosis of cell. The goal of the current study is to build an in silico homology model further to identify the structural features that influence the inhibitory activity of chromodomain-helicase-DNA-binding protein 1-like protein grounded on a variety of 103 set of compounds. GOLD program is used to carry out molecular docking studies to ascertain the binding mode of structurally varied inhibitors of chromodomain-helicase-DNA-binding protein 1-like protein. Most active residues docked with chromodomain-helicase-DNA-binding protein 1-like protein are compound 20, 103 and 22 with their GOLD Scores 90.5, 81.01 and 79.2, respectively. These docked residues exhibited substantial interaction with active site residues of the protein. Ligand-protein binding is further elucidated with the extensive hydrogen bonding and other hydrophobic interactions. Chromodomain-helicase-DNA-binding protein 1-like protein belongs to Snf2 family of proteins with conserved evolutionary function. Another interesting aspect of this study is the presence of a conserved Snf2 N-terminal domain observed in chromodomain-helicase-DNA-binding protein 1-like protein. It controls the catalytic and the helicase activity which is crucial in regulating tumor progression. A hundred nanosecond molecular dynamics simulation of docked chromodomain-helicase-DNA-binding protein 1-like illustrated a stable binding pattern of ligand in the protein’s active site. Furthermore, trajectory analysis was performed to assess various characteristics of the docked system in terms of function of time. This study pinpoints potential novel inhibitors against chromodomain-helicase-DNA-binding protein 1-like protein which have not been reported previously but are involved in the overexpression in different cancers. This finding will help to design a prospective drug for varied number of cancers.

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Acknowledgments

Authors are highly grateful to the International Foundation of Science and Higher Education Commission, Islamabad, Pakistan for funding this study.

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Authors and Affiliations

  1. Computational Biology Lab, National Center for Bioinformatics, Quaid-i-Azam University, Islamabad, Pakistan

    Sundus Iqbal, Amen Shamim & Syed Sikander Azam

  2. Department of Biochemistry, Abdul Wali Khan University Mardan, KPK, Pakistan

    Abdul Wadood

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  1. Sundus Iqbal
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  2. Amen Shamim
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  3. Syed Sikander Azam
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Correspondence to Syed Sikander Azam.

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Iqbal, S., Shamim, A., Azam, S.S. et al. Identification of potent inhibitors for chromodomain-helicase- DNA-binding protein 1-like through moleculardocking studies. Med Chem Res 25, 2924–2939 (2016). https://doi.org/10.1007/s00044-016-1712-x

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  • DOI: https://doi.org/10.1007/s00044-016-1712-x

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