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Applications of Molecular Simulation in the Discovery of Antituberculosis Drugs: A Review

[ Vol. 26 , Issue. 9 ]

Author(s):

Jian-Ping Hu, Zhi-Xiang Wu, Tao Xie, Xin-Yu Liu, Xiao Yan, Xin Sun, Wei Liu, Li Liang, Gang He, Ya Gan, Xiao-Jun Gou, Zheng Shi, Qiang Zou, Hua Wan, Hu-Bing Shi* and Shan Chang*   Pages 648 - 663 ( 16 )

Abstract:


After decades of efforts, tuberculosis has been well controlled in most places. The existing drugs are no longer sufficient for the treatment of drug-resistant Mycobacterium tuberculosis due to significant toxicity and selective pressure, especially for XDR-TB. In order to accelerate the development of high-efficiency, low-toxic antituberculosis drugs, it is particularly important to use Computer Aided Drug Design (CADD) for rational drug design. Here, we systematically reviewed the specific role of molecular simulation in the discovery of new antituberculosis drugs.

The purpose of this review is to overview current applications of molecular simulation methods in the discovery of antituberculosis drugs. Furthermore, the unique advantages of molecular simulation was discussed in revealing the mechanism of drug resistance.

The comprehensive use of different molecular simulation methods will help reveal the mechanism of drug resistance and improve the efficiency of rational drug design.

With the help of molecular simulation methods such as QM/MM method, the mechanisms of biochemical reactions catalyzed by enzymes at atomic level in Mycobacterium tuberculosis has been deeply analyzed. QSAR and virtual screening both accelerate the development of highefficiency, low-toxic potential antituberculosis drugs. Improving the accuracy of existing algorithms and developing more efficient new methods for CADD will always be a hot topic in the future. It is of great value to utilize molecular dynamics simulation to investigate complex systems that cannot be studied in experiments, especially for drug resistance of Mycobacterium tuberculosis.

Keywords:

Mycobacterium tuberculosis, molecular simulation, computer aided drug design, inhibition mechanism, drug resistance, cell wall.

Affiliation:

College of Pharmacy and Biological Engineering, Sichuan Industrial Institute of Antibiotics, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Chengdu University, Chengdu, College of Pharmacy and Biological Engineering, Sichuan Industrial Institute of Antibiotics, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Chengdu University, Chengdu, College of Pharmacy and Biological Engineering, Sichuan Industrial Institute of Antibiotics, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Chengdu University, Chengdu, Laboratory of Tumor Targeted and Immune Therapy, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, College of Pharmacy and Biological Engineering, Sichuan Industrial Institute of Antibiotics, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Chengdu University, Chengdu, College of Pharmacy and Biological Engineering, Sichuan Industrial Institute of Antibiotics, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Chengdu University, Chengdu, College of Pharmacy and Biological Engineering, Sichuan Industrial Institute of Antibiotics, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Chengdu University, Chengdu, College of Pharmacy and Biological Engineering, Sichuan Industrial Institute of Antibiotics, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Chengdu University, Chengdu, College of Pharmacy and Biological Engineering, Sichuan Industrial Institute of Antibiotics, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Chengdu University, Chengdu, College of Pharmacy and Biological Engineering, Sichuan Industrial Institute of Antibiotics, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Chengdu University, Chengdu, College of Pharmacy and Biological Engineering, Sichuan Industrial Institute of Antibiotics, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Chengdu University, Chengdu, College of Pharmacy and Biological Engineering, Sichuan Industrial Institute of Antibiotics, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Chengdu University, Chengdu, College of Pharmacy and Biological Engineering, Sichuan Industrial Institute of Antibiotics, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Chengdu University, Chengdu, College of Mathematics and Informatics, South China Agricultural University, Guangzhou, Laboratory of Tumor Targeted and Immune Therapy, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou

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