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In Silico Investigation of Traditional Chinese Medicine for Potential Lead Compounds as SPG7 Inhibitors against Coronary Artery Disease

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 stud...

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Autores principales: Chen, Kuen-Bao, Chen, Kuan-Chung, Chang, Ya-Lin, Chang, Kun-Lung, Chang, Pei-Chun, Chang, Tung-Ti, Chen, Yu-Chian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273800/
https://www.ncbi.nlm.nih.gov/pubmed/27164068
http://dx.doi.org/10.3390/molecules21050588
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author Chen, Kuen-Bao
Chen, Kuan-Chung
Chang, Ya-Lin
Chang, Kun-Lung
Chang, Pei-Chun
Chang, Tung-Ti
Chen, Yu-Chian
author_facet Chen, Kuen-Bao
Chen, Kuan-Chung
Chang, Ya-Lin
Chang, Kun-Lung
Chang, Pei-Chun
Chang, Tung-Ti
Chen, Yu-Chian
author_sort Chen, Kuen-Bao
collection PubMed
description 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.
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spelling pubmed-62738002018-12-28 In Silico Investigation of Traditional Chinese Medicine for Potential Lead Compounds as SPG7 Inhibitors against Coronary Artery Disease Chen, Kuen-Bao Chen, Kuan-Chung Chang, Ya-Lin Chang, Kun-Lung Chang, Pei-Chun Chang, Tung-Ti Chen, Yu-Chian Molecules Article 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. MDPI 2016-05-05 /pmc/articles/PMC6273800/ /pubmed/27164068 http://dx.doi.org/10.3390/molecules21050588 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Kuen-Bao
Chen, Kuan-Chung
Chang, Ya-Lin
Chang, Kun-Lung
Chang, Pei-Chun
Chang, Tung-Ti
Chen, Yu-Chian
In Silico Investigation of Traditional Chinese Medicine for Potential Lead Compounds as SPG7 Inhibitors against Coronary Artery Disease
title In Silico Investigation of Traditional Chinese Medicine for Potential Lead Compounds as SPG7 Inhibitors against Coronary Artery Disease
title_full In Silico Investigation of Traditional Chinese Medicine for Potential Lead Compounds as SPG7 Inhibitors against Coronary Artery Disease
title_fullStr In Silico Investigation of Traditional Chinese Medicine for Potential Lead Compounds as SPG7 Inhibitors against Coronary Artery Disease
title_full_unstemmed In Silico Investigation of Traditional Chinese Medicine for Potential Lead Compounds as SPG7 Inhibitors against Coronary Artery Disease
title_short In Silico Investigation of Traditional Chinese Medicine for Potential Lead Compounds as SPG7 Inhibitors against Coronary Artery Disease
title_sort in silico investigation of traditional chinese medicine for potential lead compounds as spg7 inhibitors against coronary artery disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273800/
https://www.ncbi.nlm.nih.gov/pubmed/27164068
http://dx.doi.org/10.3390/molecules21050588
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