title: Pharmacological chaperone design for reducing risk factor of Parkinson's disease from traditional chinese medicine.
abstract: Dysfunction of β -glucocerebrosidase (GCase) has no hydrolytic activity in patients of Gaucher's disease and increasing the risk factor for Parkinson's disease occurrence. Pharmacological chaperone design has been used to treat with misfolded protein in related disease, which utilized a small compound to cause protein folding correctly. This study employed the world largest traditional Chinese medicine (TCM) database for searching for potential lead compound as pharmacological chaperone, and we also performed molecular dynamics (MD) simulations to observe the stability of binding conformation between ligands and active site of GCase structure. The docking results from database screening show that N-methylmescaline and shihunine have high binding ability to GCase than tetrahydroxyazepanes. From MD simulation analysis, tetrahydroxyazepanes displayed high opportunity of ligand migration instead of our TCM candidates, and H-bonds number was decreased in the end of MD snapshot. Our result indicated that binding conformation of N-methylmescaline and shihunine remains stable during MD simulation, demonstrating that the two candidates are suitable for GCase binding and might be potential as pharmacological chaperone for GCase folding correctly.
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 Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan.
authors: Cheng-Chun
authors: CC
authors: Lee
authors: School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan ; Department of Biotechnology, Asia University, Taichung 41354, Taiwan ; China Medical University Beigang Hospital, Yunlin 65152, Taiwan ; Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Calvin Yu-Chian
authors: CY
authors: Chen