Nielsen J E, Vriend G
European Molecular Biology Laboratory, Heidelberg, Germany.
Proteins. 2001 Jun 1;43(4):403-12. doi: 10.1002/prot.1053.
pK(a) calculation methods that are based on finite difference solutions to the Poisson-Boltzmann equation (FDPB) require that energy calculations be performed for a large number of different protonation states of the protein. Normally, the differences between these protonation states are modeled by changing the charges on a few atoms, sometimes the differences are modeled by adding or removing hydrogens, and in a few cases the positions of these hydrogens are optimized locally. We present an FDPB-based pK(a) calculation method in which the hydrogen-bond network is globally optimized for every single protonation state used. This global optimization gives a significant improvement in the accuracy of calculated pK(a) values, especially for buried residues. It is also shown that large errors in calculated pK(a) values are often due to structural artifacts induced by crystal packing. Optimization of the force fields and parameters used in pK(a) calculations should therefore be performed with X-ray structures that are corrected for crystal artifacts.
基于泊松-玻尔兹曼方程有限差分法（FDPB）的pK(a)计算方法要求对蛋白质的大量不同质子化状态进行能量计算。通常，这些质子化状态之间的差异通过改变少数原子上的电荷来建模，有时通过添加或去除氢来建模，在少数情况下，这些氢的位置会进行局部优化。我们提出了一种基于FDPB的pK(a)计算方法，其中对于所使用的每个质子化状态，氢键网络都会进行全局优化。这种全局优化显著提高了计算得到的pK(a)值的准确性，特别是对于埋藏残基。研究还表明，计算得到的pK(a)值中的大误差往往是由晶体堆积引起的结构假象导致的。因此，在进行pK(a)计算时，应对用于校正晶体假象的X射线结构进行力场和参数优化。
