Misra V K, Sharp K A, Friedman R A, Honig B
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032.
J Mol Biol. 1994 Apr 29;238(2):245-63. doi: 10.1006/jmbi.1994.1285.
Salt dependent electrostatic effects play a central role in intermolecular interactions involving nucleic acids. In this paper, the finite-difference solution to the nonlinear Poisson-Boltzmann (NLPB) equation is used to evaluate the salt dependent contribution to the electrostatic binding free energy of the minor groove binding antibiotics DAPI, Hoechst 33258 and netropsin to DNA using detailed molecular structures of the complexes. For each of these systems, a treatment based on the NLPB equation accurately describes the variation of the experimentally observed binding constant with bulk salt concentration. A solvation formalism is developed in which salt effects are described in terms of three free energy contributions: the electrostatic ion-molecule interaction free energy, delta delta G degrees im; the electrostatic ion-ion interaction free energy, delta delta G degrees ii; and the entropic ion organization free energy, delta delta G degrees org. The electrostatic terms, delta delta G degrees im and delta delta G degrees ii, have both enthalpic and entropic components, while the term delta delta G degrees org is purely a cratic entropy. Each of these terms depends significantly on salt dependent changes in the counterion and coion concentrations around the DNA. In each of the systems studied, univalent ions substantially destabilize charged ligand-DNA complexes at physiological salt concentrations. This effect involves a salt dependent redistribution of counterions near the DNA. The free energy associated with the redistribution of counterions upon binding is dominated by the unfavorable change in the electrostatic ion-molecule interactions, delta delta G degrees im, rather than the change in the cratic entropy of ion organization, delta delta G degrees org. In addition, the observed slope of the salt dependence of the free energy is determined by electrostatic ion-molecule and ion-ion interactions as well as the cratic entropy of ion release. These findings are in contrast to models in which the cratic entropy of counterion release drives binding.
盐依赖的静电效应在涉及核酸的分子间相互作用中起着核心作用。在本文中，利用复合物的详细分子结构，通过非线性泊松 - 玻尔兹曼（NLPB）方程的有限差分法来评估盐对小沟结合抗生素DAPI、Hoechst 33258和纺锤菌素与DNA静电结合自由能的贡献。对于这些系统中的每一个，基于NLPB方程的处理方法都能准确描述实验观察到的结合常数随本体盐浓度的变化。本文提出了一种溶剂化形式，其中盐效应通过三种自由能贡献来描述：静电离子 - 分子相互作用自由能，ΔΔG°im；静电离子 - 离子相互作用自由能，ΔΔG°ii；以及熵离子组织自由能，ΔΔG°org。静电项ΔΔG°im和ΔΔG°ii既有焓成分又有熵成分，而ΔΔG°org项纯粹是一种有序熵。这些项中的每一项都显著依赖于DNA周围抗衡离子和共离子浓度的盐依赖变化。在每个研究的系统中，单价离子在生理盐浓度下会使带电配体 - DNA复合物显著失稳。这种效应涉及DNA附近抗衡离子的盐依赖重新分布。结合时抗衡离子重新分布所关联的自由能主要由静电离子 - 分子相互作用的不利变化ΔΔG°im主导，而非离子组织有序熵的变化ΔΔG°org。此外，观察到的自由能盐依赖性斜率由静电离子 - 分子和离子 - 离子相互作用以及离子释放的有序熵决定。这些发现与抗衡离子释放的有序熵驱动结合的模型形成对比。
