Identification of Potent Chloride Intracellular Channel Protein 1 Inhibitors from Traditional Chinese Medicine through Structure-Based Virtual Screening and Molecular Dynamics Analysis.

Chloride intracellular channel 1 (CLIC1) is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products...

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Publicado en:BioMed Research International Vol. 2017; pp. 1 - 11
Autores principales: Wang, Wei, Wan, Minghui, Liao, Dongjiang, Peng, Guilin, Xu, Xin, Yin, Weiqiang, Guo, Guixin, Jiang, Funeng, Zhong, Weide, He, Jianxing
Formato: equations & formulas research tables/charts Journal Article
Publicado: Wiley-Blackwell 9/25/2017
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 9/25/2017
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2017/4751780
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        atl: Identification of Potent Chloride Intracellular Channel Protein 1 Inhibitors from Traditional Chinese Medicine through Structure-Based Virtual Screening and Molecular Dynamics Analysis.
      aug:
        au:
          Wang, Wei
          Wan, Minghui
          Liao, Dongjiang
          Peng, Guilin
          Xu, Xin
          Yin, Weiqiang
          Guo, Guixin
          Jiang, Funeng
          Zhong, Weide
          He, Jianxing
        affil: Department of Thoracic Surgery, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
      sug:
        subj:
          Proteins Physiology
          Medicine, Chinese Traditional
          Bioinformatics
          Virtual High-Throughput Screening
          Human
          Genes
          Stomach Neoplasms Physiopathology
          Colonic Neoplasms
          Lung Neoplasms Physiopathology
          Liver Neoplasms
          Glioma
          Databases
          Patient Selection
          Ligands
          Protocols
      ab: Chloride intracellular channel 1 (CLIC1) is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent CLIC1 inhibitors from Traditional Chinese Medicine (TCM) database using structure-based virtual screening and molecular dynamics (MD) simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by X-Score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulation was employed to validate the stability of interactions between each hit and CLIC1 protein from docking simulation, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis was used to refine the virtual hits. Six TCM compounds with top MM-GBSA scores and ideal-binding models were confirmed as the final hits. Our study provides information about the interaction between TCM compounds and CLIC1 protein, which may be helpful for further experimental investigations. In addition, the top 6 natural products structural scaffolds could serve as building blocks in designing drug-like molecules for CLIC1 inhibition.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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