Teixeira Vitor H, Cunha Carlos A, Machuqueiro Miguel, Oliveira A Sofia F, Victor Bruno L, Soares Cláudio M, Baptista António M
Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, EAN, Apartado 127, 2781-901 Oeiras, Portugal.
J Phys Chem B. 2005 Aug 4;109(30):14691-706. doi: 10.1021/jp052259f.
Poisson-Boltzmann (PB) models are a fast and common tool for studying electrostatic processes in proteins, particularly their ionization equilibrium (protonation and/or reduction), often yielding quite good results when compared with more detailed models. Yet, they are conceptually very simple and necessarily approximate, their empirical character being most evident when it comes to the choice of the dielectric constant assigned to the protein region. The present study analyzes several factors affecting the ability of PB-based methods to model protein ionization equilibrium. We give particular attention to a suggestion made by Warshel and co-workers (e.g., Sham et al. J. Phys. Chem. B 1997, 101, 4458) of using different protein dielectric constants for computing the individual (site) and the pairwise (site-site) terms of the ionization free energies. Our prediction of pK(a) values for several proteins indicates that no advantage is obtained by such a procedure, even for sites that are buried and/or display large pK(a) shifts relative to the solution values. In particular, the present methodology gives the best predictions using a dielectric constant around 20, for shifted/buried and nonshifted/exposed sites alike. The similarities and differences between the PB model and Warshel's PDLD/S model are discussed, as well as the reasons behind their apparently discrepant results. The present PB model is shown to predict also good reduction potentials in redox proteins.
泊松 - 玻尔兹曼（PB）模型是研究蛋白质静电过程的一种快速且常用的工具，特别是其电离平衡（质子化和/或还原），与更详细的模型相比，通常能产生相当不错的结果。然而，它们在概念上非常简单且必然是近似的，其经验性在涉及分配给蛋白质区域的介电常数的选择时最为明显。本研究分析了影响基于PB方法模拟蛋白质电离平衡能力的几个因素。我们特别关注Warshel及其同事提出的建议（例如，Sham等人，《物理化学杂志B》，1997年，101卷，4458页），即使用不同的蛋白质介电常数来计算电离自由能的个体（位点）和成对（位点 - 位点）项。我们对几种蛋白质的pK(a)值的预测表明，即使对于相对于溶液值被掩埋和/或显示出较大pK(a)位移的位点，这种方法也没有优势。特别是，本方法使用约20的介电常数对位移/掩埋位点和未位移/暴露位点都给出了最佳预测。讨论了PB模型与Warshel的PDLD/S模型之间的异同，以及它们结果明显不同的背后原因。结果表明，当前的PB模型在预测氧化还原蛋白的还原电位方面也表现良好。
