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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| Format: | Article |
| Language: | en_US |
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MDPI AG
2016
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| Online Access: | http://hdl.handle.net/1721.1/103530 |
| _version_ | 1811070507657723904 |
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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 |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program 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 | MIT |
| 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. |
| first_indexed | 2024-09-23T08:37:08Z |
| format | Article |
| id | mit-1721.1/103530 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:37:08Z |
| publishDate | 2016 |
| publisher | MDPI AG |
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| spelling | mit-1721.1/1035302022-09-30T10:01:31Z 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 Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biology Chen, Yu-Chian 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. Taiwan. Ministry of Health and Welfare (Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019)) Asia University (ASIA102-CMU-1) Asia University (ASIA102-CMU-2) Asia University (ASIA102-CMU-3) China Medical University (CMU102-BC-9) China Medical University (Hospital (DMR-104-001) China Medical University (Hospital (Hospital (DMR-104-084) China Medical University (Hospital (Hospital (DMR-104-118) 2016-07-05T17:46:42Z 2016-07-05T17:46:42Z 2016-04 2016-04 Article http://purl.org/eprint/type/JournalArticle 1420-3049 http://hdl.handle.net/1721.1/103530 Chen, Kuen-Bao, Kuan-Chung Chen, Ya-Lin Chang, Kun-Lung Chang, Pei-Chun Chang, Tung-Ti Chang, and Yu-Chian Chen. “In Silico Investigation of Traditional Chinese Medicine for Potential Lead Compounds as SPG7 Inhibitors Against Coronary Artery Disease.” Molecules 21, no. 5 (May 5, 2016): 588. en_US http://dx.doi.org/10.3390/molecules21050588 Molecules Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf MDPI AG MDPI |
| spellingShingle | 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 |
| url | http://hdl.handle.net/1721.1/103530 |
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