Binding of small basic peptides to membranes containing acidic lipids: Theoretical models and experimental results
Binding of small basic peptides to membranes containing acidic lipids: Theoretical models and experimental results
复制标题
DOI：
10.1016/s0006-3495(96)79280-9
复制
发表时间：
1996-08-01
影响因子：
3.4
通讯作者：
McLaughlin, S
中科院分区：
文献类型：
--
作者：
BenTal, N;Honig, B;McLaughlin, S
我们直接测量了 Lys(3)、Lys(5) 和 Lys(7) 与含有酸性磷脂的囊泡的结合。当囊泡含有 33% 酸性脂质且水溶液含有 100 mM 一价盐时，这些肽结合的标准吉布斯自由能分别为 3、5 和 7 kcal/mol。随着膜中酸性脂质的摩尔％降低和/或随着盐浓度的增加，结合能降低。一些证据表明这些亲水肽不会穿透膜的极性头基区域，并且结合主要是由于静电相互作用，为了计算经典静电学的结合能，我们将非线性泊松-玻尔兹曼方程应用于磷脂双层和水溶液中碱性肽的原子模型，相互作用的静电自由能，它由带正电的肽和带负电的脂质双层之间的长程库仑吸引力产生，当肽的范德华表面和脂质双层之间存在类似于 2.5 埃（即一层水）时，短程玻恩或镜像电荷排斥力是最小的。计算出的摩尔缔合常数 K 与测量值非常吻合：K 通常比实验值小约 10 倍（即结合自由能相差约 1.5 kcal/mol）。预测的 K（或结合自由能）对溶液离子强度、膜中酸性脂质的 mol% 以及肽中碱性残基数量的依赖性与实验测量结果非常吻合。这些计算与许多含有碱性残基簇的重要蛋白质的膜结合有关。
We measured directly the binding of Lys(3), Lys(5), and Lys(7) to vesicles containing acidic phospholipids. When the vesicles contain 33% acidic lipids and the aqueous solution contains 100 mM monovalent salt, the standard Gibbs free energy for the binding of these peptides is 3, 5, and 7 kcal/mol, respectively. The binding energies decrease as the mol% of acidic lipids in the membrane decreases and/or as the salt concentration increases. Several lines of evidence suggest that these hydrophilic peptides do not penetrate the polar headgroup region of the membrane and that the binding is mainly due to electrostatic interactions, To calculate the binding energies from classical electrostatics, we applied the nonlinear Poisson-Boltzmann equation to atomic models of the phospholipid bilayers and the basic peptides in aqueous solution, The electrostatic free energy of interaction, which arises from both a long-range coulombic attraction between the positively charged peptide and the negatively charged lipid bilayer, and a short-range Born or image charge repulsion, is a minimum when similar to 2.5 Angstrom (i.e., one layer of water) exists between the van der Waals surfaces of the peptide and the lipid bilayer, The calculated molar association constants, K, agree well with the measured values: K is typically about 10-fold smaller than the experimental value (i.e., a difference of about 1.5 kcal/mol in the free energy of binding). The predicted dependence of K (or the binding free energies) on the ionic strength of the solution, the mol% of acidic lipids in the membrane, and the number of basic residues in the peptide agree very well with the experimental measurements. These calculations are relevant to the membrane binding of a number of important proteins that contain clusters of basic residues.