Institute of Molecular Biophysics+, Florida State University, Tallahassee, Florida 32306, USA.
J Phys Chem B. 2011 Aug 18;115(32):9864-72. doi: 10.1021/jp204915y. Epub 2011 Jul 26.
The observed salt dependence of charged ligand binding to polyelectrolytes, such as proteins to DNA or antithrombin to heparin, is often interpreted by means of the "oligolysine model." We review this model as derived entirely within the framework of the counterion condensation theory of polyelectrolytes with no introduction of outside assumptions. We update its comparison with experimental data on the structurally simple systems for which it was originally intended. We then compute the salt dependence of the binding free energy for a variety of protein-DNA complexes with nonlinear Poisson-Boltzmann (NLPB) simulation methods. The results of the NLPB calculations confirm the central prediction of the oligolysine model that the net charge density of DNA remains invariant to protein binding. Specifically, when a cationic protein residue penetrates the layer of counterions condensed on DNA, a counterion is released to bulk solution, and when an anionic protein residue penetrates the condensed counterion layer, an additional counterion is condensed from bulk solution. We also conclude, however, that the cumulative effect of charged protein residues distant from the binding interface makes a significant contribution to the salt dependence of binding, an observation not accommodated by the oligolysine model.
观察到带电荷配体与聚电解质（如蛋白质与 DNA 或抗凝血酶与肝素）的结合依赖于盐，这种现象通常可以用“寡聚赖氨酸模型”来解释。我们对该模型进行了综述，它完全是在聚电解质的抗衡离子凝聚理论框架内推导出来的，没有引入外部假设。我们更新了它与最初旨在用于的结构简单系统的实验数据的比较。然后，我们使用非线性泊松-玻尔兹曼（NLPB）模拟方法计算了各种蛋白质-DNA 复合物的结合自由能对盐的依赖性。NLPB 计算结果证实了寡聚赖氨酸模型的核心预测，即 DNA 的净电荷密度在蛋白质结合时保持不变。具体来说，当带正电荷的蛋白质残基穿透凝聚在 DNA 上的抗衡离子层时，一个抗衡离子会被释放到本体溶液中，而当带负电荷的蛋白质残基穿透凝聚的抗衡离子层时，会从本体溶液中额外凝聚一个抗衡离子。然而，我们还得出结论，远离结合界面的带电蛋白质残基的累积效应对结合的盐依赖性有显著贡献，这一观察结果无法用寡聚赖氨酸模型来解释。
