Identification of Potent Chloride Intracellular Channel Protein 1 Inhibitors from Traditional Chinese Medicine through Structure-Based Virtual Screening and Molecular Dynamics Analysis
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- 英文论文题名：Identification of Potent Chloride Intracellular Channel Protein 1 Inhibitors from Traditional Chinese Medicine through Structure-Based Virtual Screening and Molecular Dynamics Analysis
- 论文作者：王炜 ; Minghui Wan ; Dongjiang Liao ; Guilin Peng ; Xin Xu ; Weiqiang Yin ; Guixin Guo ; Funeng Jiang ; Weide Zhong ; Jianxing He
- 英文论文作者：Wei Wang ; Minghui Wan ; Dongjiang Liao ; Guilin Peng ; Xin Xu ; Weiqiang Yin ; Guixin Guo ; Funeng Jiang ; Weide Zhong ; Jianxing He ; Department of Thoracic Surgery ; First Affiliated Hospital of Guangzhou Medical University ; Guangzhou Institute of Respiratory Diseases & China State Key Laboratory of Respiratory Disease ; National Respiratory Disease Clinical Research Center ; Department of Radiation Oncology ; First Affiliated Hospital of Guangzhou Medical University ; National Supercomputer Center in Guangzhou ; Department of Urology ; Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics ; Guangzhou First People's Hospital ; Guangzhou Medical University
- 年：2017
- 作者机构：广州医科大学附属第一医院;Guangzhou Institute of Respiratory Diseases & China State Key Laboratory of Respiratory Disease;National Respiratory Disease Clinical Research Center;Department of Radiation Oncology, First Affiliated Hospital of Guangzhou Medical University;Department of Thoracic Surgery, First Affiliated Hospital of Guangzhou Medical University;National Supercomputer Center in Guangzhou;Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University;
- 英文论文关键词：CLIC1 ; Traditional Chinese medicine(TCM) database ; Virtual screening ; Molecular dynamics ; MM-GBSA analysis
- 会议召开时间：2017-04-08
- 会议录名称：中国生物工程学会第二届青年科技论坛暨首届青年工作委员会学术年会论文集
- 语种：英文
- 分类号：R284
- 学会代码：IGSV
- 会议名称：中国生物工程学会第二届青年科技论坛暨首届青年工作委员会学术年会
- 会议地点：中国广东广州
- 主办单位：中国生物工程学会青年工作委员会
- 学会名称：中国生物工程学会
- 页数：2
- 文件大小：24k
- 原文格式：D
- 会议级别：全国
摘要
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 re-ranked by X-score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulations 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 druglike molecules for CLIC1 inhibition.
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 re-ranked by X-score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulations 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 druglike molecules for CLIC1 inhibition.
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 re-ranked by X-score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulations 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 druglike molecules for CLIC1 inhibition.
引文