ON THE MAGNITUDE OF THE ELECTROSTATIC CONTRIBUTION TO LIGAND-DNA INTERACTIONS
ON THE MAGNITUDE OF THE ELECTROSTATIC CONTRIBUTION TO LIGAND-DNA INTERACTIONS
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DOI：
10.1073/pnas.92.10.4691
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发表时间：
1995-05-09
影响因子：
11.1
通讯作者：
HONIG, B
中科院分区：
文献类型：
--
作者：
MISRA, VK;HONIG, B
基于非线性泊松-玻尔兹曼方程的模型用于研究简单嵌入配体 3,8-二氨基-6-苯基菲啶与 DNA 的结合自由能的静电贡献。我们发现非线性泊松-玻尔兹曼模型准确地描述了插层时观察到的 3,8-二氨基-6-苯基菲啶的 pK(a) 位移的绝对大小及其随大量盐浓度的变化。由于 pK(a) 位移与配体的带电和中性形式的总静电结合自由能直接相关，计算的准确性意味着对结合的静电贡献也被准确预测。静电对配体-DNA 结合的贡献，其中静电结合自由能被描述为配体对 DNA 的库仑吸引力与结合时溶剂破坏之间的平衡。与高电荷核酸相关的长程库仑力为阳离子配体与 DNA 的相互作用提供了强大的驱动力。然而，这些有利的静电相互作用在很大程度上被配体和 DNA 结合时溶剂化的不利变化所补偿。配体-DNA复合物的形成从纯溶剂中去除了结合界面上的带电基团和极性基团，同时置换了核酸周围的盐，因此，总静电结合自由能相当小，因此，非极性相互作用，例如紧密堆积和疏水力，必须在配体-DNA稳定性中发挥重要作用。
A model based on the nonlinear Poisson-Boltzmann equation is used to study the electrostatic contribution to the binding free energy of a simple intercalating ligand, 3,8-diamino-6-phenylphenanthridine, to DNA. We find that the nonlinear Poisson-Boltzmann model accurately describes both the absolute magnitude of the pK(a) shift of 3,8-diamino-6-phenylphenanthridine observed upon intercalation and its variation with bulk salt concentration, Since the pK(a) shift is directly related to the total electrostatic binding free energy of the charged and neutral forms of the ligand, the accuracy of the calculations implies that the electrostatic contributions to binding are accurately predicted as well, Based on our results, we have developed a general physical description of the electrostatic contribution to ligand-DNA binding in which the electrostatic binding free energy is described as a balance between the coulombic attraction of a ligand to DNA and the disruption of solvent upon binding, Long-range coulombic forces,associated with highly charged nucleic acids provide a strong driving force for the interaction of cationic ligands with DNA, These favorable electrostatic interactions are, however, largely compensated for by unfavorable changes in the solvation of both the ligand and the DNA upon binding. The formation of a ligand-DNA complex removes both charged and polar groups at the binding interface from pure solvent while it displaces salt from around the nucleic acid, As a result, the total electrostatic binding free energy is quite small, Consequently, nonpolar interactions, such as tight packing and hydrophobic forces, must play a significant role in ligand-DNA stability.