Exploring Peptide-Membrane Interactions with Coarse-Grained MD Simulations
Exploring Peptide-Membrane Interactions with Coarse-Grained MD Simulations
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DOI：
10.1016/j.bpj.2011.02.041
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发表时间：
2011-04-20
影响因子：
3.4
通讯作者：
Sansom, Mark S. P.
中科院分区：
文献类型：
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作者：
Hall, Benjamin A.;Chetwynd, Alan P.;Sansom, Mark S. P.
α-螺旋肽与脂类双层的相互作用是我们理解生物膜组织和稳定性的物理化学原理的核心。改变膜内α-螺旋的位置或方向的突变，或改变α-螺旋插入膜的概率的突变，都可以改变一系列膜蛋白的功能。我们描述了一种相对粗粒度的分子动力学模拟方法，该方法基于脂双层在α-螺旋多肽存在下的自组装，这使得我们能够模拟跨膜螺旋插入。我们对合成模型多肽(WALP23和LS3)的现有实验数据验证了该方法。基于模拟的对插入囊性纤维化跨膜调节器衍生的双层螺旋的表观自由能的估计与已发表的转位蛋白介导的插入数据很好地相关。比较来自自组装模拟的插入表观自由能与模型肽的粗粒分子动力学平均作用力势的值，以及与转位介导的囊性纤维化跨膜调节子衍生肽的插入，表明螺旋插入双分子层的非平衡模型。
The interaction of alpha-helical peptides with lipid bilayers is central to our understanding of the physicochemical principles of biological membrane organization and stability. Mutations that alter the position or orientation of an a-helix within a membrane, or that change the probability that the alpha-helix will insert into the membrane, can alter a range of membrane protein functions. We describe a comparative coarse-grained molecular dynamics simulation methodology, based on self-assembly of a lipid bilayer in the presence of an a-helical peptide, which allows us to model membrane transmembrane helix insertion. We validate this methodology against available experimental data for synthetic model peptides (WALP23 and LS3). Simulation-based estimates of apparent free energies of insertion into a bilayer of cystic fibrosis transmembrane regulator-derived helices correlate well with published data for translocon-mediated insertion. Comparison of values of the apparent free energy of insertion from self-assembly simulations with those from coarse-grained molecular dynamics potentials of mean force for model peptides, and with translocon-mediated insertion of cystic fibrosis transmembrane regulator-derived peptides suggests a nonequilibrium model of helix insertion into bilayers.