Electrostatic effects in homeodomain-DNA interactions
Electrostatic effects in homeodomain-DNA interactions
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DOI：
10.1006/jmbi.1996.0842
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发表时间：
1997-03-28
影响因子：
5.6
通讯作者：
McCammon, JA
中科院分区：
文献类型：
--
作者：
Fogolari, F;Elcock, AH;McCammon, JA
我们在这里报告的调查的作用，静电在同源结构域DNA相互作用的技术基础上使用周围的泊松-玻尔兹曼方程。在本发明的情况下，这种研究是特别有意义的，因为与以前用这种方法研究的其它蛋白质相反，同源结构域是一种小的、高电荷的蛋白质，其在结合DNA时形成广泛的离子对。我们已经研究了盐的依赖性的结合常数为特定的协会和非特定协会的各种模型。结果表明，与Manning和Record提出的模型一致，反离子释放熵占结合自由能的盐依赖性的很大一部分，尽管这可能是由于偶然取消了其他贡献项。一些特定的同源结构域突变体的热力学效应也进行了研究，并部分合理化在有利的静电相互作用的主要goove的DNA。缔合自由能的温度依赖性的调查表明，随着温度的升高，静电的贡献变得越来越有利。然而，对于这个特定的系统，似乎没有显着的静电贡献的Δ（Δ C-p）的协会。最后，当同源结构域从DNA移动约一德拜长度时的相互作用自由能的分析表明，纯静电力能够将同源结构域引导到与DNA结合的部分正确的方向。(C)出版社：Academic Press Limited。
We report here an investigation of the role of electrostatics in homeodomain-DNA interactions using techniques based around the use of the Poisson-Boltzmann equation. in the present case such a study is of particular interest, since in contrast to other proteins previously studied with this method, the homeodomain is a small, highly charged protein that forms extensive ion pairs upon binding DNA. We have investigated the salt dependence of the binding constant for specific association and for a variety of models for non-specific association. The results indicate that, in Line with the models proposed by Manning and Record, the entropy of counterion release accounts for a significant fraction of the salt dependence of the binding free energy, though this is perhaps due to fortuitous cancellation of other contributing terms. The thermodynamic effects of a number of specific homeodomain mutants were also investigated, and partly rationalized in terms of favorable electrostatic interactions in the major goove of DNA. Investigation of the temperature-dependence of the free energy of association indicates that the electrostatic contributions become increasingly favorable as the temperature rises. For this particular system, however, there appears to be no significant electrostatic contribution to the Delta(Delta C-p) of association. Finally, an analysis of the free energy of interaction when the homeodomain is moved ca one Debye length from the DNA suggests that pure electrostatic forces are able to steer the homeodomain into a partially correct orientation for binding to the DNA. (C) 1997 Academic Press Limited.