Pharmacological Chaperone Design for Reducing Risk Factor of Parkinson’s Disease from Traditional Chinese Medicine
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ECAM.2014.830490.pdf
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4.29 MB
Format
Adobe PDF
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cbfd436e5ef45302154dbf89582ba802
Author(s)
Huang, Hung-Jin
Lee, Cheng-Chun
Chen, Calvin Yu-Chian
Date Issued
January 2014
Journal
Evidence-Based Complementary and Alternative Medicine
Publisher
Hindawi Publishing Corporation
Citation
Huang, Hung-Jin, Cheng-Chun Lee, and Calvin Yu-Chian Chen. “Pharmacological Chaperone Design for Reducing Risk Factor of Parkinson’s Disease from Traditional Chinese Medicine.” Evidence-Based Complementary and Alternative Medicine 2014 (2014): 1–12.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1155/2014/830490
