Understanding the physical basis of the salt dependence of the electrostatic binding free energy of mutated charged ligand-nucleic acid complexes
Understanding the physical basis of the salt dependence of the electrostatic binding free energy of mutated charged ligand-nucleic acid complexes
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DOI：
10.1016/j.bpc.2011.02.010
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发表时间：
2011-06-01
影响因子：
3.8
通讯作者：
Fenley, Marcia O.
中科院分区：
文献类型：
--
作者：
Harris, Robert C.;Bredenberg, Johan H.;Fenley, Marcia O.
通过泊松-玻尔兹曼方程PBE预测生物分子复合物的静电结合自由能Δ G（el）相对于1：1盐浓度的对数d（Δ G（el））/d（In[NaCl]）SK的导数与更简单的德拜-休克尔方程DHE非常相似，因为PBE预测的SK中依赖于电介质界面细节的项与长程静电相互作用的贡献相比很小。这些事实允许人们使用简化的电荷模型沿着与DHE获得SK的预测，其与PBE和实验结合数据高度相关。DHE为基础的模型，这是从广义玻恩模型，解释了SK和Δ G（el）之间缺乏相关性的存在下的介电不连续性，这与流行的使用这种假设的相关性解析实验结合自由能成静电和非静电组件冲突。此外，DHE模型还为SK与各种经验量之间的相关性提供了明确的理由，如离子对的数量，界面上的配体电荷，库仑结合自由能和复合物组分上的电荷的乘积，但这些相关性很弱，质疑它们的有用性。(C)2011 Elsevier B. V.保留所有权利。
The predictions of the derivative of the electrostatic binding free energy of a biomolecular complex, Delta G(el), with respect to the logarithm of the 1:1 salt concentration, d(Delta G(el))/d(In[NaCl]), SK, by the Poisson-Boltzmann equation, PBE, are very similar to those of the simpler Debye-Huckel equation, DHE, because the terms in the PBE's predictions of SK that depend on the details of the dielectric interface are small compared to the contributions from long-range electrostatic interactions. These facts allow one to obtain predictions of SK using a simplified charge model along with the DHE that are highly correlated with both the PBE and experimental binding data. The DHE-based model developed here, which was derived from the generalized Born model, explains the lack of correlation between SK and Delta G(el) in the presence of a dielectric discontinuity, which conflicts with the popular use of this supposed correlation to parse experimental binding free energies into electrostatic and nonelectrostatic components. Moreover, the DHE model also provides a clear justification for the correlations between SK and various empirical quantities, like the number of ion pairs, the ligand charge on the interface, the Coulomb binding free energy, and the product of the charges on the complex's components, but these correlations are weak, questioning their usefulness. (C) 2011 Elsevier B.V. All rights reserved.