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. 1. Introduction Gaucher’s disease (GD) is caused by mutations in the GBA gene encoding β-glucocerebrosidase (GCase), which leads to inherited glucocerebrosidase deficiency. Because the mutated GCase has no function of hydrolytic activity, the deficient activity of GCase cannot transport from the endoplasmic reticulum (ER) to lysosomes [1]; this phenomenon impaired intracellular transport and contributes to defects of metabolism in fibroblasts of patients [2]. Subsequently, both glucosylceramide (GluCer) and glucosylsphingosine (GluSph) accumulate in macrophages of various organs [3], such as spleen, liver, lungs, bone marrow, and brain [4]; clinical feature of GD disease reveals deposition of undigested subtracts in lysosome of macrophages. In several clinical cases of Gaucher’s disease, symptoms of central nervous system (CNS) disorder existed in patient’s brain [5]. GD is the most prevalent lysosomal storage diseases [6]; some lines of evidence; indicated that reducing GCase activity is associated with Parkinson’s disease (PD) [7, 8] and the mutation of GCase has high risk factor for PD occurrence [9]. Parkinson’s disease (PD) is one of the common CNS diseases of neurodegenerative disorders affecting 2% of older adults after the age of 65 [10], which is the second common neuron degenerated disease after Alzheimer’s
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