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用高温淬火分子动力学模拟方法研究了甲硫氨酸脑啡肽(Metenkephalin)在真空中的构象性质.经聚类分析和能量优化得到了十三个低能构象,并与吗啡进行了空间拟合.模拟结果表明,Metenkephalin是一种构象柔性大的多肽分子,可具有多种构象,主要为Gly2-Gly3和Gly3-Phe4之间的β折叠型式.大多数的结构具有由氢键连接两个末端残基所形成的假大环,侧链和芳香环定位在假大环的同侧.模拟结果还表明,模型最大的特征是:酪氨酸残基中的氨基N相当于吗啡中哌啶环上的季胺N,酪氨酸残基中的酚环相当于吗啡中的酚环,苯丙氨酸残基中的芳香环相当于吗啡中环己烯环.此肽与吗啡在空间结构(药效基团)上非常相似,都满足阿片受体的要求.所以,它们可作用于同一受体.该模型也能为具有阿片效能的肽和非肽配体的药效团设计提供帮助.
The conformational properties of metenkephalin in vacuum were investigated by high-temperature quenching molecular dynamics simulations. Thirteen low-energy conformations were obtained by cluster analysis and energy optimization and spatially fitted with morphine The simulation results show that Metenkephalin is a kind of polypeptide with large conformational flexibility and multiple conformations, and mainly consists of β-sheet between Gly2-Gly3 and Gly3-Phe4 Most structures have the structure of hydrogen bonds between the two ends The pseudo macrocycles, side chains and aromatic rings formed by the residues are located on the same side of the pseudocapacity.The simulation results also show that the most prominent feature of the model is that the amino group N in the tyrosine residue corresponds to the piperidine ring in morphine On the quaternary ammonium N, tyrosine residues in the phenolic ring equivalent to the phenolic ring in morphine, phenylalanine residue in the aromatic ring equivalent to the cyclohexene ring in morphine. This peptide and morphine in the spatial structure (medicine Which are very similar to opioid receptors and therefore act on the same receptor.The model can also aid in the design of pharmacophore with opioid peptides and non-peptide ligands.