Molecular Dynamics Simulations of the Interactions of Kinin Peptides with an Anionic POPG Bilayer
Molecular Dynamics Simulations of the Interactions of Kinin Peptides with an Anionic POPG Bilayer
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DOI：
10.1021/la104046z
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发表时间：
2011-04-05
期刊：
影响因子：
3.9
通讯作者：
Mukhopadhyay, Chaitali
中科院分区：
文献类型：
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作者：
Manna, Moutusi;Mukhopadhyay, Chaitali
我们已经进行了分子动力学模拟的肽激素缓激肽（BK）和它的片段des-Arg 9-BK在阴离子脂质双层的存在下，其目的是描绘与其生物活性的作用机制。从最初的水性环境开始，这两种肽迅速吸附并稳定在细胞表面上。而BK表现出更强的相互作用与膜，并喜欢留在界面上，des-Arg 9-BK，与C-末端Arg的损失，进一步渗透。非均质的脂质-水界面在原本固有的柔性肽中诱导β-转角样结构。在膜结合状态下，我们观察到BK中的C-末端β-转角形成，而对于缺失Arg 9的des-Arg 9-BK，转角形成发生在肽的中间。碱性Arg残基通过与带电脂质头基的强静电相互作用将肽锚在双层上。模拟与不同的起始取向的肽相对于双层表面导致相同的观察，即相对定位的肽在膜表面上，更深的渗透的des-Arg 9-BK，并形成转向结构。与结合肽相邻的脂质头基变得基本上倾斜，导致肽接触区域附近的双层变薄，并增加附近脂质的无序程度。同样，由于与肽的氢键，相邻脂质的极性头部表现出相当低的柔性。从早期的实验结果证实，我们的研究结果提供了重要的信息，脂质环境如何促进肽的方向/构象和肽如何适应环境。
We have performed molecular dynamics simulations of peptide hormone bradykinin (BK) and its fragment des-Arg9-BK in the presence of an anionic lipid bilayer, with an aim toward delineating the mechanism of action related to their bioactivity. Starting from the initial aqueous environment, both of the peptides are quickly adsorbed and stabilized on the cell surface. Whereas BK exhibits a stronger interaction with the membrane and prefers to stay on the interface, des-Arg9-BK, with the loss of C-terminal Arg, penetrates further. The heterogeneous lipid-water interface induces beta-turn-like structure in the otherwise inherently flexible peptides. In the membrane-bound state, we observed C-terminal beta-turn formation in BK, whereas for des-Arg9-BK, with the deletion of Arg9, turn formation occurred in the middle of the peptide. The basic Arg residues anchor the peptide to the bilayer by strong electrostatic interactions with charged lipid headgroups. Simulations with different starting orientations of the peptides with respect to the bilayer surface lead to the same observations, namely the relative positioning of the peptides on the membrane surface, deeper penetration of the des-Arg9-BK, and the formation of turn structures. The lipid headgroups adjacent to the bound peptides become substantially tilted, causing bilayer thinning near the peptide contact region and increase the degree of disorder in nearby lipids. Again, because of hydrogen bonding with the peptide, the neighboring lipid's polar heads exhibit considerably reduced flexibility. Corroborating findings from earlier experiments, our results provide important information about how the lipid environment promotes peptide orientation/conformation and how the peptide adapts to the environment.