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Finding Inhibitors of Mutant Superoxide Dismutase-1 for Amyotrophic Lateral Sclerosis Therapy from Traditional Chinese Medicine
Superoxide dismutase type 1 (SOD1) mutations cause protein aggregation and decrease protein stability, which are linked to amyotrophic lateral sclerosis (ALS) disease. This research utilizes the world's largest traditional Chinese medicine (TCM) database to search novel inhibitors of mutant SOD...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052194/ https://www.ncbi.nlm.nih.gov/pubmed/24963318 http://dx.doi.org/10.1155/2014/156276 |
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author | Huang, Hung-Jin Chang, Tung-Ti Chen, Hsin-Yi Chen, Calvin Yu-Chian |
author_facet | Huang, Hung-Jin Chang, Tung-Ti Chen, Hsin-Yi Chen, Calvin Yu-Chian |
author_sort | Huang, Hung-Jin |
collection | PubMed |
description | Superoxide dismutase type 1 (SOD1) mutations cause protein aggregation and decrease protein stability, which are linked to amyotrophic lateral sclerosis (ALS) disease. This research utilizes the world's largest traditional Chinese medicine (TCM) database to search novel inhibitors of mutant SOD1, and molecular dynamics (MD) simulations were used to analyze the stability of protein that interacted with docked ligands. Docking results show that hesperidin and 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) have high affinity to mutant SOD1 and then dopamine. For MD simulation analysis, hesperidin and THSG displayed similar value of RMSD with dopamine, and the migration analysis reveals stable fluctuation at the end of MD simulation time. Interestingly, distance between the protein and ligand has distinct difference, and hesperidin changes the position from initial binding site to the other place. In flexibility of residues analysis, the secondary structure among all complexes does not change, indicating that the structure are not affect ligand binding. The binding poses of hesperidin and THSG are similar to dopamine after molecular simulation. Our result indicated that hesperidin and THSG might be potential lead compound to design inhibitors of mutant SOD1 for ALS therapy. |
format | Online Article Text |
id | pubmed-4052194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-40521942014-06-24 Finding Inhibitors of Mutant Superoxide Dismutase-1 for Amyotrophic Lateral Sclerosis Therapy from Traditional Chinese Medicine Huang, Hung-Jin Chang, Tung-Ti Chen, Hsin-Yi Chen, Calvin Yu-Chian Evid Based Complement Alternat Med Research Article Superoxide dismutase type 1 (SOD1) mutations cause protein aggregation and decrease protein stability, which are linked to amyotrophic lateral sclerosis (ALS) disease. This research utilizes the world's largest traditional Chinese medicine (TCM) database to search novel inhibitors of mutant SOD1, and molecular dynamics (MD) simulations were used to analyze the stability of protein that interacted with docked ligands. Docking results show that hesperidin and 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) have high affinity to mutant SOD1 and then dopamine. For MD simulation analysis, hesperidin and THSG displayed similar value of RMSD with dopamine, and the migration analysis reveals stable fluctuation at the end of MD simulation time. Interestingly, distance between the protein and ligand has distinct difference, and hesperidin changes the position from initial binding site to the other place. In flexibility of residues analysis, the secondary structure among all complexes does not change, indicating that the structure are not affect ligand binding. The binding poses of hesperidin and THSG are similar to dopamine after molecular simulation. Our result indicated that hesperidin and THSG might be potential lead compound to design inhibitors of mutant SOD1 for ALS therapy. Hindawi Publishing Corporation 2014 2014-05-18 /pmc/articles/PMC4052194/ /pubmed/24963318 http://dx.doi.org/10.1155/2014/156276 Text en Copyright © 2014 Hung-Jin Huang et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Huang, Hung-Jin Chang, Tung-Ti Chen, Hsin-Yi Chen, Calvin Yu-Chian Finding Inhibitors of Mutant Superoxide Dismutase-1 for Amyotrophic Lateral Sclerosis Therapy from Traditional Chinese Medicine |
title | Finding Inhibitors of Mutant Superoxide Dismutase-1 for Amyotrophic Lateral Sclerosis Therapy from Traditional Chinese Medicine |
title_full | Finding Inhibitors of Mutant Superoxide Dismutase-1 for Amyotrophic Lateral Sclerosis Therapy from Traditional Chinese Medicine |
title_fullStr | Finding Inhibitors of Mutant Superoxide Dismutase-1 for Amyotrophic Lateral Sclerosis Therapy from Traditional Chinese Medicine |
title_full_unstemmed | Finding Inhibitors of Mutant Superoxide Dismutase-1 for Amyotrophic Lateral Sclerosis Therapy from Traditional Chinese Medicine |
title_short | Finding Inhibitors of Mutant Superoxide Dismutase-1 for Amyotrophic Lateral Sclerosis Therapy from Traditional Chinese Medicine |
title_sort | finding inhibitors of mutant superoxide dismutase-1 for amyotrophic lateral sclerosis therapy from traditional chinese medicine |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052194/ https://www.ncbi.nlm.nih.gov/pubmed/24963318 http://dx.doi.org/10.1155/2014/156276 |
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