铁皮石斛多糖与Toll样受体4互作机制的计算模拟

Computational Simulation of Interaction Mechanism between Dendrobium officinale Polysaccharide and Toll⁃like Receptor 4

为研究铁皮石斛多糖(Dendrobium officinale polysaccharide,DOP)具有免疫活性片段的结构特征及与Toll样受体4(Toll⁃like receptor 4,TLR4)的相互作用机制,基于对TLR4结合腔的亲疏水性分析,将DOP寡糖的分为疏水片段筛选和亲水片段筛选,通过分子对接和分子动力学模拟,分析作用最强的DOP片段的结构特征及与TLR4的相互作用机制。结果表明,找到作用最强的DOP七糖片段,具有与经典底物脂多糖相似的结合模式,其中疏水性四糖片段结合在疏水结合腔,亲水性三糖片段结合在电正性区域。具有潜在免疫活性的铁皮石斛多糖可以由乙酰基修饰的疏水四糖片段和没有乙酰基修饰的亲水三糖片段组成,主要通过氢键和疏水作用与TLR4进行相互作用,发挥免疫活性。

In this study,a computational simulation was conducted in order to investigate the structural char⁃acteristics of immunoactivity fragments of Dendrobium officinale polysaccharide(DOP)and the mechanism of interaction with Toll⁃like receptor 4(TLR4).Based on hydrophobic analysis of the TLR4 binding pocket,DOP oligosaccharides were divided into hydrophobic fragment screening and hydrophilic fragment screening.Molecular docking and molecular dynamics simulation were employed to analyze the structural characteristics of the most powerful DOP fragments and their interaction mechanism with TLR4.The results unveiled a heptas⁃accharide DOP fragment with the strongest activity,exhibiting a binding mode similar to that of classical sub⁃strate lipopolysaccharide.The hydrophobic tetrasaccharide fragment was bound to the hydrophobic binding cavity,and the hydrophilic trisaccharide fragment was bound to the positively charged region.In conclusions,the potentially immunomodulatory DOP was composed of an acetyl⁃modified hydrophobic tetrasaccharide frag⁃ment and a non⁃acetylated hydrophilic trisaccharide fragment,which mainly interacts with TLR4 through hy⁃drogen bonding and hydrophobic interaction.