title: In silico identification of potent pancreatic triacylglycerol lipase inhibitors from traditional Chinese medicine.
abstract: Pancreatic triacylglycerol lipase (PNLIP) are primary lipases that are critical for triacylglyceride digestion in human. Since reduced metabolism of triacylglyceride might be a plausible concept for weight loss, we screened for potential PNLIP inhibitors from traditional Chinese medicine (TCM) with the aim to identify weight loss candidate compounds. TCM candidates Aurantiamide, Cnidiadin, and 2-hexadecenoic acid exhibited higher Dock Scores than the commercial drug Orlistat, and were also predicted to have inhibitory characteristics against PNLIP using constructed MLR (R(2) = 0.8664) and SVM (R(2) = 0.9030) models. Molecular dynamics indicated that the TCM-PNLIP complexes formed were stable. We identified that the PNLIP binding site has several residues that can serve as anchors, and a hydrophobic corridor that provides additional stability to the complex. Aurantiamide, Cnidiadin, and 2-hexadecenoic acid all have features that correspond to these binding site features, indicating their potential as candidates for PNLIP inhibitors. The information presented in this study may provide helpful insights to designing novel weight-control drugs.
authors.affiliation: Department of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Chen
authors.forename: Su-Sen
authors.initials: SS
authors.lastname: Chang
authors.forename: Calvin Yu-Chian
authors.initials: CY
authors.lastname: Chen
mesh_terms: D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D004791:Enzyme Inhibitors / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008024:Ligands; D016014:Linear Models; D008049:Lipase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008516:Medicine, Chinese Traditional; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010179:Pancreas / Q000201:enzymology*; D017433:Protein Structure, Secondary; D060388:Support Vector Machine
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D008049:Lipase