title: Finding inhibitors of mutant superoxide dismutase-1 for amyotrophic lateral sclerosis therapy from traditional chinese medicine.
abstract: 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.
authors: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
authors: Hung-Jin
authors: HJ
authors: Huang
authors: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
authors: Tung-Ti
authors: TT
authors: Chang
authors: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan.
authors: Hsin-Yi
authors: HY
authors: Chen
authors: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan ; School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan.
authors: Calvin Yu-Chian
authors: CY
authors: Chen