Free energy profile of the interaction between a monomer or a dimer of protegrin-1 in a specific binding orientation and a model lipid bilayer.
Free energy profile of the interaction between a monomer or a dimer of protegrin-1 in a specific binding orientation and a model lipid bilayer.
复制标题
特定结合方向的 protegrin-1 单体或二聚体与模型脂质双层之间相互作用的自由能曲线。
DOI：
10.1021/jp909640g
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Kaznessis,Yiannis
中科院分区：
文献类型：
--
作者：
Vivcharuk,Victor;Kaznessis,Yiannis
利用分子动力学（MD）模拟和泊松-玻尔兹曼计算，确定了阳离子β-发夹抗菌肽蛋白-1 （PG1）的单体或二聚体在脂质双分子层上特定结合取向的吸附自由能。双分子层由阴离子棕榈酰油酰磷脂酰甘油（POPG）和棕榈酰油酰磷脂酰乙醇胺（POPE）组成，比例为1:3 （POPG/POPE）。PG1被认为通过结合在细菌的膜上杀死细菌。在那里，它形成了分解细菌的孔。在这里，我们着重于结合的热力学。特别是，我们探索了从脂质双分子层中释放反离子在吸附PG1的单体或二聚体形式时的作用。生成平衡系统的22个4-ns长的MD轨迹，以确定单体和二聚体的自由能分布，作为肽与膜表面之间距离的函数。两种体系分别在11种不同的膜分离下进行了MD模拟，一种是PG1，另一种是PG1二聚体，只有单体和二聚体的特定取向，而不考虑肽的熵变化。为了计算每个肽/膜系统的平均力势，使用了一种约束MD和热力学积分的变体。我们观察到PG1二聚体更有利于与POPG/POPE膜结合。用一种简单的方法将PG1 -膜结合常数与自由能谱联系起来，预测PG1 -膜的吸附自由能为- 2.4±0.8 kcal/mol。相应的pg1 -二聚体-膜结合常数计算为- 3.5±1.1 kcal/mol。对MD模拟的自由能谱进行了广泛的分析，并与泊松-玻尔兹曼理论的结果进行了比较。我们发现肽-膜的吸引力主要是由于在POPG/POPE脂质双分子层中释放反离子而引起的熵增加。
The free energies of adsorption of the monomer or dimer of the cationic β-hairpin antimicrobial peptide protegrin-1 (PG1) in a specific binding orientation on a lipid bilayer are determined using molecular dynamics (MD) simulations and Poisson−Boltzmann calculations. The bilayer is composed of anionic palmitoyl-oleoyl-phosphatidylglycerol (POPG) and palmitoyl-oleoyl-phosphatidylethanolamine (POPE) with ratio 1:3 (POPG/POPE). PG1 is believed to kill bacteria by binding on their membranes. There, it forms pores that lyse the bacteria. Herein we focus on the thermodynamics of binding. In particular, we explore the role of counterion release from the lipid bilayer upon adsorption of either the monomeric or the dimeric form of PG1. Twenty-two 4-ns-long MD trajectories of equilibrated systems are generated to determine the free energy profiles for the monomer and dimer as a function of the distance between the peptide(s) and the membrane surface. The MD simulations are conducted at 11 different separations from the membrane for each of the two systems, one with PG1, the second with a PG1 dimer of only a specific orientation of the monomer and dimer without taking into account the change of entropy for the peptide. To calculate the potential of mean force for each peptide/membrane system, a variant of constrained MD and thermodynamic integration is used. We observed that PG1 dimer binds more favorably to the POPG/POPE membrane. A simple method for relating the free energy profile to the PG1−membrane binding constant is employed to predict a free energy of adsorption of −2.4 ± 0.8 kcal/mol. A corresponding PG1-dimer−membrane binding constant is calculated as −3.5 ± 1.1 kcal/mol. Free energy profiles from MD simulation were extensively analyzed and compared with results of Poisson−Boltzmann theory. We find the peptide−membrane attraction to be dominated by the entropy increase due to the release of counterions in a POPG/POPE lipid bilayer.