Mehler E L
Department of Physiology/Biophysics, Mt Sinai Medical Center, New York, NY 10029.
Protein Eng. 1990 Apr;3(5):415-7. doi: 10.1093/protein/3.5.415.
Two recent approaches for calculating pK shifts in proteins are compared. The first of these uses Coulomb's law with a distance-dependent dielectric permittivity, epsilon (r), to model the screening effects of the environment, and the second uses a finite difference approach to solve Poisson's equation. It is shown that an explicit form of epsilon (r) which has been fitted to experimentally determined values of the dielectric permittivity in a range from 1 to 21 A can be approximated by a linear form in the functionally significant range of charge separations of approximately 3-10 A, but for distances greater than 10 A the effective permittivity is strongly nonlinear. A statistical analysis of the errors in calculated pK shifts due to electrostatic interactions between charges with separations greater than 10 A shows that there are only marginal differences in reliability between using Coulomb's law with an appropriate form of epsilon (r) or the finite difference approach for solving Poisson's equation. Thus it is concluded that pK shifts can be calculated just as well, and with considerably less effort, using Coulomb's law.
比较了两种最近用于计算蛋白质中pK位移的方法。第一种方法使用具有距离依赖性介电常数ε(r)的库仑定律来模拟环境的屏蔽效应，第二种方法使用有限差分法来求解泊松方程。结果表明，一种已根据1至21埃范围内介电常数的实验测定值拟合的ε(r)显式形式，在电荷分离约3至10埃的功能重要范围内可以近似为线性形式，但对于大于10埃的距离，有效介电常数具有强烈的非线性。对电荷间距大于10埃时由于静电相互作用导致的计算pK位移误差进行的统计分析表明，使用具有适当形式ε(r)的库仑定律或求解泊松方程的有限差分法，在可靠性方面只有微小差异。因此得出结论，使用库仑定律可以同样好地计算pK位移，而且工作量要少得多。
