Helix-helix interactions in lipid bilayers
Helix-helix interactions in lipid bilayers
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DOI：
10.1016/s0006-3495(96)79498-5
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发表时间：
1996-12-01
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;Honig, B
使用连续介质模型，我们计算了两个α-螺旋在三种环境中的静电相互作用自由能：水相，低介电烷烃相，和一个简单的代表性的脂质双层。如在先前的工作中发现的，在水相中的螺旋-螺旋相互作用是相当弱的，因为溶剂屏蔽，和轻微排斥，因为伴随螺旋组装的去溶剂化效应。相反，在假设的烷烃相中，相互作用可能相当强，因为去溶剂化效应基本上不存在，并且因为螺旋-螺旋相互作用没有被很好地屏蔽。在这种类型的环境中，反平行螺旋取向强烈优于平行取向。在以前的工作中，我们发现，自由能惩罚与埋螺旋末端在双层是相当高的，这就是为什么终端往往突出到溶剂中。在这些条件下，静电相互作用被溶剂强烈屏蔽;事实上，末端从双层的两个表面突出几埃就足以使它们的相互作用几乎完全消失。这种效果与螺旋偶极子的经典模型一致，其中偶极矩由位于两端的点电荷表示。我们的研究结果表明，与以前的模型一致，螺旋聚集没有显着的非特异性驱动力，因此，膜蛋白折叠必须由特定的相互作用，如紧密包装和盐桥和氢键的形成。
Using a continuum model, we calculated the electrostatic interaction free energy between two alpha-helices in three environments: the aqueous phase, a low dielectric alkane phase, and a simple representation of a lipid bilayer. As was found in previous work, helix-helix interactions in the aqueous phase are quite weak, because of solvent screening, and slightly repulsive, because of desolvation effects that accompany helix assembly. In contrast, the interactions can be quite strong in a hypothetical alkane phase because desolvation effects are essentially nonexistent and because helix-helix interactions are not well screened. In this type of environment, the antiparallel helix orientation is strongly favored over the parallel orientation. In previous work we found that the free energy penalty associated with burying helix termini in a bilayer is quite high, which is why the termini tend to protrude into the solvent. Under these conditions the electrostatic interaction is strongly screened by solvent; indeed, it is sufficient for the termini to protrude a few angstroms from the two surfaces of the bilayer for their interaction to diminish almost completely The effect is consistent with the classical model of the helix dipole in which the dipole moment is represented by point charges located at either terminus. Our results suggest, in agreement with previous models, that there is no significant nonspecific driving force for helix aggregation and, hence, that membrane protein folding must be driven by specific interactions such as close packing and salt-bridge and hydrogen bond formation.