We have carried out molecular dynamics simulations of the naturally occurring protegrin PG-1 peptide and two of its mutants, PC-9 and PC-13 in the presence of a dodecyl-phosphocholine (DPC) micelle. The effects of mutations that disrupt the β-sheet structure in the case of PC-9 and reduce the charge at the C-terminus in the case of PC-13 are analyzed. It is found that the surface-bound conformations of the peptides are severely affected by both mutations. PG-1 exhibits a conformation in which the C-terminus and the β-hairpin turn interact strongly with the micelle lipid head groups, while its N-terminal strand bends away from the micelle and resides in the aqueous region; PC-13 exhibits strong interactions with the micelle at its N-terminus as well as the β-hairpin turn region, while retaining a much more compact conformation than PG-1; PC-9 achieves a highly distorted conformation relative to the homologous PG-1 structure, which allows both its termini and the β-hairpin region to interact with the micelle. These significant differences observed as a result of seemingly minor mutations to the sequences of the three peptides are explained in terms of the interplay between residue charges, structural rigidity and amphiphilic interactions. Conservative inferences are made bridging these biophysical interactions and the pharmacological profiles of the peptides.

中文翻译：

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三种 protegrin 型抗菌肽的分子动力学模拟：末端电荷、β-折叠结构和两亲相互作用之间的相互作用

我们在十二烷基磷酸胆碱 (DPC) 胶束存在的情况下，对天然存在的 protegrin PG-1 肽及其两个突变体 PC-9 和 PC-13 进行了分子动力学模拟。分析了在 PC-9 的情况下破坏 β-折叠结构和在 PC-13 的情况下减少 C 端电荷的突变的影响。发现肽的表面结合构象受到两种突变的严重影响。PG-1 表现出一种构象，其中 C 端和 β-发夹转角与胶束脂质头部基团强烈相互作用，而其 N 端链弯曲远离胶束并驻留在水区；PC-13 在其 N 端和 β-发夹转角区域与胶束表现出强烈的相互作用，同时保持比 PG-1 更紧凑的构象；PC-9 相对于同源 PG-1 结构实现了高度扭曲的构象，这使得其末端和 β-发夹区域都可以与胶束相互作用。由于三种肽的序列看似微小的突变而观察到的这些显着差异是根据残基电荷、结构刚性和两亲相互作用之间的相互作用来解释的。保守的推论将这些生物物理相互作用和肽的药理学特征联系起来。由于三种肽的序列看似微小的突变而观察到的这些显着差异是根据残基电荷、结构刚性和两亲相互作用之间的相互作用来解释的。进行了保守推断，将这些生物物理相互作用和肽的药理学特征联系起来。由于三种肽的序列看似微小的突变而观察到的这些显着差异是根据残基电荷、结构刚性和两亲相互作用之间的相互作用来解释的。保守的推论将这些生物物理相互作用和肽的药理学特征联系起来。