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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。
Chinese medicine oligopeptide is one of the key components of traditional Chinese medicine to play a pharmacological effect. To study systematically the composition of Chinese medicine oligopeptide and its efficacy is the key to the study of the material basis and mechanism of action. Based on the computer-aided hydrolysis and molecular docking techniques, this study aims to elucidate the components of hypotensive oligopeptides and predict the potential antagonistic activity of endothelin receptor A (ETA) based on Chinese traditional medicine Soybean. In this paper, a virtual structural database is constructed by collecting the conserved protein sequences in soybeans, performing simulated digestion and hydrolysis of proteins based on computer-assisted hydrolysis, and hydrolyzing the resulting oligopeptides. Subsequently, the study constructed a pharmacophore model of ETA peptide antagonist, including one hydrophobic feature, one negative charge center, one aromatic ring signature, and five exclusion volumes. At the same time, the three-dimensional structure model of ETA protein was constructed by homology modeling method and used to study the molecular docking. The ETA antagonistic activity of the compound was evaluated by consistent scoring. By constructing a pharmacophore model of ETA peptide antagonist, three-dimensional protein structure of homology modeling and molecular docking model, 27 oligopeptide molecules that may have potential ETA antagonistic activity were predicted. This article further analyzes the key amino acid GLN165, combined with the literature, indicating its importance of antagonist activity. The computer-aided hydrolysis method can effectively simulate the hydrolysis of traditional Chinese medicine proteins with known sequence structure. Combined with the molecular simulation model, the potential biological activities of Chinese medicine oligopeptides can be further identified. This study provides a methodological basis for the rapid and efficient study of the active mechanism of peptides derived from traditional Chinese medicine.