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


Wang Wei123ORCID,Wan Minghui45,Liao Dongjiang23,Peng Guilin123,Xu Xin123,Yin Weiqiang123,Guo Guixin6,Jiang Funeng7,Zhong Weide7,He Jianxing123ORCID


1. Department of Thoracic Surgery, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China

2. Guangzhou Institute of Respiratory Diseases and China State Key Laboratory of Respiratory Disease, Guangzhou 510120, China

3. National Respiratory Disease Clinical Research Center, Guangzhou 510000, China

4. Southern Medical University, Guangzhou 510000, China

5. Department of Radiation Oncology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China

6. National Supercomputer Center in Guangzhou, Guangzhou 510000, China

7. Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou 510180, China


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.


National Natural Science Foundation of China


Hindawi Limited


General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine







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