title: In Silico Investigation of Traditional Chinese Medicine for Potential Lead Compounds as SPG7 Inhibitors against Coronary Artery Disease.
abstract: Coronary artery disease (CAD) is the most common cause of heart attack and the leading cause of mortality in the world. It is associated with mitochondrial dysfunction and increased level of reactive oxygen species production. According to the Ottawa Heart Genomics Study genome-wide association study, a recent research identified that Q688 spastic paraplegia 7 (SPG7) variant is associated with CAD as it bypasses the regulation of tyrosine phosphorylation of AFG3L2 and enhances the processing and maturation of SPG7 protein. This study aims to identify potential compounds isolated from Traditional Chinese Medicines (TCMs) as potential lead compounds for paraplegin (SPG7) inhibitors. For the crystallographic structure of paraplegin, the disordered disposition of key amino acids in the binding site was predicted using the PONDR-Fit protocol before virtual screening. The TCM compounds saussureamine C and 3-(2-carboxyphenyl)-4(3H)-quinazolinone, have potential binding affinities with stable H-bonds and hydrophobic contacts with key residues of paraplegin. A molecular dynamics simulation was performed to validate the stability of the interactions between each candidate and paraplegin under dynamic conditions. Hence, we propose these compounds as potential candidates as lead drug from the compounds isolated from TCM for further study in drug development process with paraplegin protein for coronary artery disease.
authors.affiliation: Department of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, Taiwan. d3510@mail.cmuh.org.tw.|School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan. d3510@mail.cmuh.org.tw.|Department of Anesthesiology, China Medical University Hospital, Taichung 40447, Taiwan. d3510@mail.cmuh.org.tw.
authors.forename: Kuen-Bao
authors.initials: KB
authors.lastname: Chen
authors.affiliation: School of Pharmacy, China Medical University, Taichung 40402, Taiwan. 9818chen@gmail.com.
authors.forename: Kuan-Chung
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Department of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, Taiwan. midwives0336@yahoo.com.tw.
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Chang
authors.affiliation: Department of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, Taiwan. kuen90@yahoo.com.tw.|Department of Pharmacy, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan. kuen90@yahoo.com.tw.
authors.forename: Kun-Lung
authors.initials: KL
authors.lastname: Chang
authors.affiliation: Department of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, Taiwan. peichun.chang@gmail.com.
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Chang
authors.affiliation: School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan. ycc929@mit.edu.|Department of Chinese Pediatrics, China Medical University Hospital, Taichung 40402, Taiwan. ycc929@mit.edu.
authors.forename: Tung-Ti
authors.initials: TT
authors.lastname: Chang
authors.affiliation: Department of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, Taiwan. tchang0604@yahoo.com.tw.|Research Center for Chinese Medicine and Acupuncture, China Medical University, Taichung 40402, Taiwan. tchang0604@yahoo.com.tw.|Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan. tchang0604@yahoo.com.tw.|Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. tchang0604@yahoo.com.tw.
authors.forename: Yu-Chian
authors.initials: YC
authors.lastname: Chen
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D001216:Asparagine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics*; D018360:Crystallography, X-Ray; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009154:Mutation; D052999:Quinazolinones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D052999:Quinazolinones; C000595384:saussureamine C; D001216:Asparagine; D008666:Metalloendopeptidases; C112889:SPG7 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities
keywords: Traditional Chinese Medicine (TCM); docking; molecular dynamics (MD) simulation; spastic paraplegia 7 (SPG7)