基于计算机辅助水解的中药大豆寡肽的ETA拮抗活性预测(1)
[摘要] 中药寡肽是中药发挥药效的关键组分之一，系统地研究中药寡肽的组成及其药效是中药物质基础及作用机制研究的关键。该研究拟基于计算机辅助水解和分子对接等模拟技术，以中药大豆为研究载体，解析其降压寡肽成分，并预测其潜在的内皮素受体A(endothelin receptor A，ETA)拮抗活性。该文通过收集大豆中的储存蛋白序列，基于计算机辅助水解方法进行蛋白的模拟消化水解，并将水解获得的寡肽构建虚拟结构数据库。随后该研究构建了ETA肽类拮抗剂的药效团模型，包括1个疏水特征、1个负电中心、1个芳环特征和5个排除体积。同时，利用同源模建方法构建ETA的蛋白三维结构模型，并将其用于分子对接研究，采用一致性打分评价化合物的ETA拮抗活性。通过构建ETA肽类拮抗剂的药效团模型、同源模建的三维蛋白结构以及分子对接模型，共预测获得27条可能具有潜在ETA拮抗活性的寡肽分子。该文进一步分析关键氨基酸GLN165，并结合文献，说明其对拮抗剂活性的重要性。计算机辅助水解方法可以高效地对已知序列结构的中药蛋白进行模拟水解，结合分子模拟模型，能进一步辨识中药寡肽潜在的生物学活性。该研究为快速、高效开展中药来源的肽类物质的活性机制研究提供了方法学依据。
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[关键词] 计算机辅助水解； 寡肽； 大豆； 內皮素受体A； 药效团； 同源模建； 分子对接
[Abstract] Oligopeptides are one of the the key pharmaceutical effective constituents of traditional Chinese medicine(TCM). Systematic study on composition and efficacy of TCM oligopeptides is essential for the analysis of material basis and mechanism of TCM. In this study， the potential anti-hypertensive oligopeptides from Glycine max and their endothelin receptor A (ETA) antagonistic activity were discovered and predicted based on in silico technologies.Main protein sequences of G. max were collected and oligopeptides were obtained using in silico gastrointestinal tract proteolysis. Then， the pharmacophore of ETA antagonistic peptides was constructed and included one hydrophobic feature， one ionizable negative feature， one ring aromatic feature and five excluded volumes. Meanwhile， three-dimensional structure of ETA was developed by homology modeling methods for further docking studies. According to docking analysis and consensus score， the key amino acid of GLN165 was identified for ETA antagonistic activity. And 27 oligopeptides from G. max were predicted as the potential ETA antagonists by pharmacophore and docking studies.In silico proteolysis could be used to analyze the protein sequences from TCM. According to combination of in silico proteolysis and molecular simulation， the biological activities of oligopeptides could be predicted rapidly based on the known TCM protein sequence. It might provide the methodology basis for rapidly and efficiently implementing the mechanism analysis of TCM oligopeptides.
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[Key words] in silico proteolysis； oligopeptides； Glycine max； ETA； pharmacophore； homology modeling； docking
中药蛋白是中药中一类常见的活性物质，具有明显而特殊的药理活性[1]。从两千多年前阿胶的应用，到水蛭素的制备和大豆多肽的上市，中药蛋白和生物活性肽的应用具有悠久的历史，已有大量的药性、药理和临床数据。而中药蛋白具有物理化学性质不稳定、易水解和易氧化的特点，因此，基于传统的中药化学方法，通过对中药蛋白提取分离酶解获取中药活性肽，往往具有分离困难、耗时费力的特点。而计算机辅助水解是基于生物信息学方法，预测蛋白质序列在特定蛋白酶或化学物质在给定条件下的切割位点的技术，该技术具有快速高效可靠的寡肽预测能力[2]，已较为广泛的应用于食品工业研究[3-4]。, 百拇医药(乔连生 蒋芦荻 雒刚刚 路芳 陈艳昆 王灵芝 李贡宇 张燕玲)
, http://www.100md.com
[关键词] 计算机辅助水解； 寡肽； 大豆； 內皮素受体A； 药效团； 同源模建； 分子对接
[Abstract] Oligopeptides are one of the the key pharmaceutical effective constituents of traditional Chinese medicine(TCM). Systematic study on composition and efficacy of TCM oligopeptides is essential for the analysis of material basis and mechanism of TCM. In this study， the potential anti-hypertensive oligopeptides from Glycine max and their endothelin receptor A (ETA) antagonistic activity were discovered and predicted based on in silico technologies.Main protein sequences of G. max were collected and oligopeptides were obtained using in silico gastrointestinal tract proteolysis. Then， the pharmacophore of ETA antagonistic peptides was constructed and included one hydrophobic feature， one ionizable negative feature， one ring aromatic feature and five excluded volumes. Meanwhile， three-dimensional structure of ETA was developed by homology modeling methods for further docking studies. According to docking analysis and consensus score， the key amino acid of GLN165 was identified for ETA antagonistic activity. And 27 oligopeptides from G. max were predicted as the potential ETA antagonists by pharmacophore and docking studies.In silico proteolysis could be used to analyze the protein sequences from TCM. According to combination of in silico proteolysis and molecular simulation， the biological activities of oligopeptides could be predicted rapidly based on the known TCM protein sequence. It might provide the methodology basis for rapidly and efficiently implementing the mechanism analysis of TCM oligopeptides.
, http://www.100md.com
[Key words] in silico proteolysis； oligopeptides； Glycine max； ETA； pharmacophore； homology modeling； docking
中药蛋白是中药中一类常见的活性物质，具有明显而特殊的药理活性[1]。从两千多年前阿胶的应用，到水蛭素的制备和大豆多肽的上市，中药蛋白和生物活性肽的应用具有悠久的历史，已有大量的药性、药理和临床数据。而中药蛋白具有物理化学性质不稳定、易水解和易氧化的特点，因此，基于传统的中药化学方法，通过对中药蛋白提取分离酶解获取中药活性肽，往往具有分离困难、耗时费力的特点。而计算机辅助水解是基于生物信息学方法，预测蛋白质序列在特定蛋白酶或化学物质在给定条件下的切割位点的技术，该技术具有快速高效可靠的寡肽预测能力[2]，已较为广泛的应用于食品工业研究[3-4]。, 百拇医药(乔连生 蒋芦荻 雒刚刚 路芳 陈艳昆 王灵芝 李贡宇 张燕玲)