Free-energy determinants of alpha-helix insertion into lipid bilayers
Free-energy determinants of alpha-helix insertion into lipid bilayers
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DOI：
10.1016/s0006-3495(96)79744-8
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发表时间：
1996-04-01
影响因子：
3.4
通讯作者：
Honig, B
中科院分区：
文献类型：
--
作者：
BenTal, N;BenShaul, A;Honig, B
详细介绍了有助于聚丙氨酸ct-螺旋从水相转移到脂质双层的各种自由能项。与以前的工作一致，发现疏水效应提供了螺旋插入的主要驱动力，然而，也确定了一个相当大小的相反的效果，并归因于大的自由能惩罚与转移到低介电环境的双层的肽氢键的去溶剂化。脂质扰动的影响，以及与螺旋固定在双层的熵损失也进行了评估。膜结合的25聚体聚丙氨酸螺旋的两种构型被发现比水相中的孤立螺旋的自由能低，第一种对应于垂直插入的情况，其中螺旋末端从双层的每一侧突出。第二个最小值是水平插入的情况下，螺旋吸附在双层的表面上。计算的自由能最小值与相关系统的最新测量结果非常一致，对于两个插入过程，都获得了由螺旋末端不满足的氢键基团去溶剂化产生的大自由能垒。如果假设螺旋末端通过与极性侧链形成氢键而被“封端”，则插入的障碍显著降低。对于未封端的螺旋，我们的结果支持最近提出的模型，其中螺旋通过首先吸附在膜表面上，然后使一个末端“摆动”以穿透双层，
A detailed treatment is provided of the various free-energy terms that contribute to the transfer of a polyalanine ct-helix from the aqueous phase into lipid bilayers. In agreement with previous work, the hydrophobic effect is found to provide the major driving force for helix insertion, However, an opposing effect of comparable magnitude is also identified and is attributed to the large free-energy penalty associated with the desolvation of peptide hydrogen bonds on transfer to the low dielectric environment of the bilayer. Lipid perturbation effects as well as the entropy loss associated with helix immobilization in the bilayer are also evaluated. Two configurations of a membrane-bound 25mer polyalanine helix were found to be lower in free energy than the isolated helix in the aqueous phase, The first corresponds to the case of vertical insertion, in which a helix terminus protrudes from each side of the bilayer. The second minimum is for the case of horizontal insertion, for which the helix is adsorbed upon the surface of the bilayer. The calculated free-energy minima are found to be in good agreement with recent measurements of related systems, Large free-energy barriers resulting from desolvation of unsatisfied hydrogen-bonding groups al the helix termini are obtained for both insertion processes. The barriers for insertion are significantly reduced if the helix termini are assumed to be ''capped'' through the formation of hydrogen bonds with polar sidechains, For uncapped helices, our results support recently proposed models in which helices are inserted by first adsorbing on the membrane surface and then having one terminus ''swing around'' so as to penetrate the bilayer,