title: The inhibition of folylpolyglutamate synthetase (folC) in the prevention of drug resistance in Mycobacterium tuberculosis by traditional Chinese medicine.
abstract: Tuberculosis (TB) is an infectious disease caused by many strains of mycobacteria, but commonly Mycobacterium tuberculosis. As a possible method of reducing the drug resistance of M. tuberculosis, this research investigates the inhibition of Folylpolyglutamate synthetase, a protein transcript from the resistance association gene folC. After molecular docking to screen the traditional Chinese medicine (TCM) database, the candidate TCM compounds, with Folylpolyglutamate synthetase, were selected by molecular dynamics. The 10,000 ps simulation in association with RMSD analysis and total energy and structural variation defined the protein-ligand interaction. The selected TCM compounds Saussureamine C, methyl 3-O-feruloylquinate, and Labiatic acid have been found to inhibit the activity of bacteria and viruses and to regulate immunity. We also suggest the possible pathway in protein for each ligand. Compared with the control, similar interactions and structural variations indicate that these compounds might have an effect on Folylpolyglutamate synthetase. Finally, we suggest Saussureamine C is the best candidate compound as the complex has a high score, maintains its structural composition, and has a larger variation value than the control, thus inhibiting the drug resistance ability of Mycobacterium tuberculosis.
authors: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan.
authors: Tzu-Chieh
authors: TC
authors: Hung
authors: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan ; School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan ; Department of Anesthesiology, China Medical University Hospital, Taichung 40447, Taiwan.
authors: Kuen-Bao
authors: KB
authors: Chen
authors: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan ; School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan ; Department of Neurosurgery, China Medical University Hospital, No. 2, Yude Road, North District, Taichung 40447, Taiwan.
authors: Wen-Yuan
authors: WY
authors: Lee
authors: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan ; School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan ; Research Center for Chinese Medicine & Acupuncture, China Medical University, Taichung 40402, Taiwan ; Human Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan.
authors: Calvin Yu-Chian
authors: 0000-0003-3306-250X
authors: CY
authors: Chen
mesh_terms: D001216:Asparagine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D064267:Intrinsically Disordered Proteins / Q000378:metabolism; D008024:Ligands; D008516:Medicine, Chinese Traditional; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology*; D010453:Peptide Synthases / Q000037:antagonists & inhibitors*; D011622:Pterins / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D064267:Intrinsically Disordered Proteins; D008024:Ligands; D011622:Pterins; C000595384:saussureamine C; C000978:dihydropteroate; D001216:Asparagine; D010453:Peptide Synthases; C023103:folylpolyglutamate synthetase