Ben-Tal N, Honig B
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
Biophys J. 1996 Dec;71(6):3046-50. doi: 10.1016/S0006-3495(96)79498-5.
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.
使用连续介质模型，我们计算了在三种环境中两条α螺旋之间的静电相互作用自由能：水相、低介电常数的烷烃相以及脂质双层的简单表示。正如在先前的工作中所发现的，由于溶剂屏蔽作用，水相中螺旋 - 螺旋相互作用相当弱，并且由于螺旋组装时伴随的去溶剂化效应而略显排斥。相比之下，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不存在，并且螺旋 - 螺旋相互作用没有得到很好的屏蔽。在这种环境类型中，反平行螺旋取向比平行取向更受青睐。在先前的工作中我们发现，将螺旋末端埋入双层中所伴随的自由能惩罚相当高，这就是为什么末端往往会突出到溶剂中。在这些条件下，静电相互作用被溶剂强烈屏蔽；实际上，对于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减弱。这种效应与螺旋偶极子的经典模型一致，在该模型中偶极矩由位于任一末端的点电荷表示。我们的结果表明，与先前的模型一致，不存在显著的非特异性螺旋聚集驱动力，因此，膜蛋白折叠必定由诸如紧密堆积、盐桥和氢键形成等特异性相互作用驱动。
