Predicting the rate enhancement of protein complex formation from the electrostatic energy of interaction.
Predicting the rate enhancement of protein complex formation from the electrostatic energy of interaction.
复制标题
从相互作用的静电能预测蛋白质复合物形成的速率增强。
DOI：
10.1006/jmbi.1999.2615
复制
发表时间：
1999
影响因子：
5.6
通讯作者：
G. Schreiber
中科院分区：
文献类型：
--
作者：
Tzvia Selzer;G. Schreiber
蛋白质的结合速率由扩散决定，但可以通过有利的静电力来增强。这里，对以下蛋白质对的相互作用静电能与蛋白质复合物形成动力学之间的关系进行了分析：水蛭素-凝血酶、乙酰胆碱酯酶-束蛋白和芽孢杆菌RNA酶-芽孢杆菌星，以及这些蛋白质的一组点突变体。使用计算机模拟软件包 DelPhi，将相互作用的静电能计算为复合物静电能与两个单独蛋白质的能量总和之间的差值。将计算出的相互作用静电能与实验确定的缔合率进行比较。 1 kcal/mol 的库仑相互作用能可将缔合速率提高 2.8 倍，与所分析的蛋白质复合物或突变体无关。使用与理论计算相同的基本方程，还可以根据缔合速率常数的盐依赖性来确定相互作用的静电能。对绘制的相互作用静电能与实验确定的缔合 ln（速率）进行绘制的布朗斯台德分析表明，两者之间存在线性关系，β 值接近 1。这被解释为过渡态的能量根据静电相互作用能而变化，拟合了缔合反应的二态模型。根据静电相互作用能计算静电速率增强可用作设计具有改变的缔合速率和亲和力的蛋白质复合物的强大工具。
The rate of association of proteins is dictated by diffusion, but can be enhanced by favorable electrostatic forces. Here the relationship between the electrostatic energy of interaction, and the kinetics of protein-complex formation was analyzed for the protein pairs of: hirudin-thrombin, acetylcholinesterase-fasciculin and barnase-barstar, and for a panel of point mutants of these proteins. Electrostatic energies of interaction were calculated as the difference between the electrostatic energy of the complex and the sum of the energies of the two individual proteins, using the computer simulation package DelPhi. Calculated electrostatic energies of interaction were compared to experimentally determined rates of association. One kcal/mol of Coulombic interaction energy increased the rate of association by a factor of 2.8, independent of the protein-complex or mutant analyzed. Electrostatic energies of interaction were also determined from the salt dependence of the association rate constant, using the same basic equation as for the theoretical calculation. A Brönsted analysis of the electrostatic energies of interactions plotted versus experimentally determined ln(rate)s of association shows a linear relation between the two, with a beta value close to 1. This is interpreted as the energy of the transition state varies according to the electrostatic interaction energy, fitting a two state model for the association reaction. Calculating electrostatic rate enhancement from the electrostatic interaction energy can be used as a powerful tool to design protein complexes with altered rates of association and affinities.
影响因子：
3.4
作者：
KOZACK, RE;DMELLO, MJ;SUBRAMANIAM, S
通讯作者：
SUBRAMANIAM, S
影响因子：
56.9
作者：
RYDEL, TJ;RAVICHANDRAN, KG;FENTON, JW
通讯作者：
FENTON, JW
蛋白质弛豫对蛋白质电荷-电荷相互作用和介电常数的影响。
影响因子：
3.4
作者：
Sham,YY;Muegge,I;Warshel,A
通讯作者：
Warshel,A