In Silico Identification of Potent Pancreatic Triacylglycerol Lipase Inhibitors from Traditional Chinese Medicine
In Silico Identification of Potent Pancreatic Triacylglycerol Lipase Inhibitors from Traditional Chinese Medicine
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DOI：
10.1371/journal.pone.0043932
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发表时间：
2012-09-06
期刊：
影响因子：
3.7
通讯作者：
Chen, Calvin Yu-Chian
中科院分区：
文献类型：
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作者：
Chen, Kuan-Yu;Chang, Su-Sen;Chen, Calvin Yu-Chian
胰三酰甘油脂肪酶（PNLIP）是人体内对甘油三酯消化至关重要的主要脂肪酶。由于降低甘油三酯的代谢可能是减肥的一个合理的概念，我们从传统中药（TCM）中筛选潜在的PNLIP抑制剂，目的是确定减肥候选化合物。中药候选物橙黄酰胺、蛇床子素和2-十六碳烯酸表现出比商业药物奥利司他更高的Dock评分，并且还使用构建的MLR（R-2 = 0.8664）和SVM（R-2 = 0.9030）模型预测对PNLIP具有抑制特性。分子动力学研究表明，所形成的TCM-PNLIP复合物是稳定的。我们发现PNLIP结合位点具有几个可以作为锚的残基，以及为复合物提供额外稳定性的疏水走廊。橙黄酰胺、蛇床子素和2-十六碳烯酸都具有对应于这些结合位点特征的特征，表明它们作为PNLIP抑制剂的候选物的潜力。本研究提供的信息可能为设计新型体重控制药物提供有用的见解。
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.